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.
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.
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.
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 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.