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Hand Transplantation: Current Status
November
2003.
I. Position of the American Society for Surgery of the Hand November
2003
W.P. Andrew Lee, MD
Dennis B. Phelps, MD
David M. Lichtman, MD
Hand transplantation has been performed since September of 1998. Preliminary
clinical experience based on 14 patients has underscored the importance
of patient motivation and compliance, intensive hand therapy, and close
post-transplantation surveillance. Acceptable functional and cosmetic
outcomes, particularly for bilateral amputees, have been achieved and
are similar to hand replantation at equivalent levels. However, major
return of two-point discrimination or intrinsic muscle function is not
to be expected.
At present, ongoing heavy immunosuppression is required for allograft
survival with unknown long-term risks. Although there have been no life-threatening
adverse events, complications include allograft rejection and loss, tissue
necrosis, and osteomyelitis. Furthermore, the effects of chronic rejection
on the allograft function and survival have not yet been determined.
Because there are many significant contraindications to both the surgical
procedure and the immunosuppressive protocol, careful pre-operative,
medical and psychological screening is mandatory.
In summary, hand transplantation is still an experimental procedure
that may enhance the function and/or appearance of carefully selected
patients. Further research and progress in transplant immunology are
needed before it can be considered a consistently safe and efficacious
practice.
September 2001
William P. Cooney, M.D.
Vincent R. Hentz, M.D.
Past Presidents of the ASSH
At the recent conference
of the International Federation of Societies for Surgery of the Hand
(IFSSH) in June 2001, information related to ten patients with upper
limb composite tissue transfer (hand transplantation) was reported. The
first patient, a 48-year-old New Zealand businessman, had surgery in
Lyon, France, in September of 1998 with an international multi-discipline
team. (2) (3) However, he failed to maintain the needed immune suppression
medication post-operatively and when chronic rejection was present, had
his transplanted hand amputated on February 2, 2001, in London by Dr.
Nadley Hakim, one of the original team members. (4) Other patients with
hand transplantations were reported from United States (N=2), China (N=3),
Italy (N=1), France (N=1), Malaysia (N=1), and Austria (N=1) (including
one bilateral hand-forearm transplant). They have had either too short
follow-up or inadequate data to evaluate the preliminary outcomes. (5)
(6) (7) Two hand transplantations (included in those listed above) have
been performed in the United States at Louisville, Kentucky, at the Jewish
Hospital, one reported with a year follow-up. This first patient, a 38-year-old
emergency medical technician, has had continued “transplant
success” as reported in November 2000. (8) A viable limb with reported
improving function and sensation at a protective level appears to be
present. Continuation of intermittent problems related to immune suppression
has been noted. The second limb transplant has also been successful from
a viability perspective, but continues to be faced with ongoing evidence
of chronic rejection, currently controlled with immunologic suppressive
medication.
As hand surgeons and members
of the American Society for Surgery of the Hand, we must ask, “What do we currently know of the expected
outcome and risks associated with hand transplantation?” “Is
this an operative procedure that we should recommend to an inquiring
patient?”
- Hand surgeons clearly possess the
needed technical skills to perform a successful hand or upper limb
transplantation as evidenced by the experience in limb replantation.
- Upper limb transplantation is now occurring in several areas throughout
the world.
- Advances in organ transplant (in particular, donor-related kidney
and liver with careful tissue HLA matching) have demonstrated improved
organ and patient survival in many life-threatening conditions. Success
in transplantation of solid organs has steadily improved both technically
and with improved immune suppression.
- Public perception and expectations are high, yet they are without
a clear understanding of the inherent risks of these procedures, both
acute risks and chronic immune suppression risks.
- We know that the hand is a complex organ of nerves,
muscle, tendon, and vessels covered by an immune intolerant skin.
Both humoral and cell mediated immune suppression is required. (9)
While hand transplants have been contrasted to kidney transplants,
a transplanted hand is not equivalent to any parenchymal tissue such
as the kidney or liver. (10) (11) (12) And while a comparison of
a hand transplant to a kidney transplant as equal with respect to
the “improved quality of
life”,
statistics and analysis clearly demonstrate that kidney transplants
save lives when one appreciates that with sustained renal dialysis,
there is a mortality rate of 21%.
How do we judge the success of hand transplants?
At this point in time, the metrics of success are not clear. (1) (10)
(11) Most agree that hand transplant success should be measured at
several levels. The first level of success is sustained revascularization
without rejection, now approaching two and half years with controlled
untoward events. The second level of success is a limb with sensibility,
proprioception, and central acceptance. The third level is the sum
of the associated risks of infection, tumor, and other complications
associated with immune suppression, counterbalanced against the potential
gain of a functioning hand. Finally, function of that vital organ of
sensation and communication must be restored sufficiently so that the
patient has the perception that his or her new hand is a natural part
of the recipient’s body. While the digits of the transplanted
hand will move and provide pinch and grasp because of the connections
to the extrinsic forearm muscles, movement resulting from independent
action of the transplanted intrinsic muscles has not been observed. Furthermore,
it is not clear that sensibility, so essential to hand expression and
advanced manual skills, will be present. The hand is considered by many
to be a representative mirror of the mind. (11) It must provide coordinated
bimanual skills. It must reflect central perceptions of coordinated,
integrated meaning. From most observations of the results of composite
tissue transplantation to date, the measurement of function of the human
hand transplantation at this level has not been convincingly demonstrated.
Animal models have been extensively
studied, and the results are not encouraging. Lee and Mathes have presented
many of the current concerns. (13) Jensen and Mackinnon have reviewed
over 250 publications on the subject of results of limb allograft transplantation
in experimental models. (14) Failure rates are beyond acceptable limits.
(15) (16) A successful transplant in animal experimental models remains
a challenge simply because of the large amounts of immune suppression
required for survival of the transplant. The complications of such medications,
at least in animal models, are currently overwhelming. (17) (18) (19)
(20) It appears at the present time nearly impossible to provide a viable
limb in the experimental models without significant risks from the immune
suppressive medications. Post transplant risks in animals including acute
rejection, medication toxicity (both nephrotoxicity and neurotoxicity),
and infection from opportunistic organisms remain significant challenges.
Despite disappointing results in the pig and primate, hopeful research
continues. (21)
Most authorities believe that these same risks are also present in the
human model. Renal transplants have an average of 1.5 septic episodes
per year, and 80% have at least one serious infectious episode within
the first year post transplant. (22) (23) Malignant tumors related to
immune suppression are reported between 8-20%, with carcinomas of the
skin and lips at 30%. (24) (25) Finally, historical data on renal and
liver transplants indicate that the overall survival at fifteen years
ranges between 30 - 60% depending upon the age of donor, HLA matching,
age and disease status of the donor, and time from transplant. (26) (27)
Recognizing these facts related to single organ transplantation, there
must also be concern that a hand transplant might develop chronic rejection
and therefore need to have the transplantation procedure repeated eight
to ten years from the index procedure to continue to provide the intended
purpose. The potential need for a second transplant, combined with the
risk of long-term immune suppression, is important historical information
that must be presented to a potential hand transplant recipient.
Ethical concerns must also be considered
in the delicate balance of risk and reward when evaluating a patient
for limb transplant. (28) What is the patient’s ability to understand the risks and make appropriate
judgments? Are the patient’s expectations realistic? Is the patient’s
psyche prepared for rejection events, repeated control of infectious
episodes, the daily required immune suppression medications, the concern
of the unknown related to ultimate function and potential chronic rejection?
How good is this “quality of life” with a new limb when daily
medications are required to maintain its viability? Can a limb be easily
removed (amputated) if both surgeon and patient recognized that chronic
rejection is occurring with so much personal time and effort invested
by both the surgeon and patient? Mr. Hallam and his surgeons struggled
over this issue for many months before the limb was finally amputated
in England. (4)
The transplanted hand, like the transplanted pancreas
or a vocal cord, may provide improved quality of life, but the impact
of a transplanted hand has not been objectively measured. Hand transplant
may improve the patient’s psyche, family interactions, and even
give a sense of fullness. However, before hand transplants can move
forward to the potential that they represent (and that potential is
acknowledged to be very great), these procedures should achieve a greater
measure of success 1) in sustained animal models; 2) with compatible
HLA matching of potential donor to the recipient; 3) with improved
bench to bedside immune suppression without requirements of long-term
immune treatment; and 4) with recipient tissue tolerance alone or with
low risk immune suppression.
We applaud the studious approach of the current
pioneering investigators of hand transplantation but strongly encourage
them to proceed slowly, cautiously, and with measured concern of the
risk and benefits to man. For those that wish to go forward with any
type of composite tissue transfer, it is important that transplant teams
be developed that are experienced in large organ transplants, aware of
advances in immune suppression medications, and include hand surgeons
within such teams who not only bring microsurgical skills but also the
ability to provide a clear understanding to the potential recipient a
knowledge of hand function by which success may be measured. At this
time, the ASSH continues to urge great caution and a measured approach
to the patient requesting a limb transplant. We encourage all surgeons
to await the outcomes of the current human experimental studies before
additional combined trials are considered. The public, especially those
with traumatic loss of limb, must be carefully counseled and advised
regarding the substantial risks to limb and life associated with these
procedures to date.
© 2007 American Society for Surgery of the Hand
Developed by the ASSH Public Education Committee
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