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for motor and sensory outcomes of lower extremity VCA, and patient outcomes post-transplant may be
more akin to individuals with peripheral nerve injuries (i.e., foot drop in the setting of peroneal nerve
[26]
damage) .

Overall, the less intricate nature of lower extremity motor function may mean that allotransplantation has
greater potential for restoring normal levels of function than has been shown with VCA of the hand. Yet,
the more straightforward function of the lower extremity is also why lower extremity prosthetics are more
effective than upper extremity prosthetics at re-approximating the functional demands of the native limb.
Further, it is unclear how weight-bearing factors come into this discussion, as the upper limb is not subject
to the same loads that burden the lower limb. Whether lower extremity allografts are capable of meeting the
long-term demands that prosthetics are designed for has also yet to be explored. At the very least, VCA of
the lower extremity may offer the possibility of converting from an above-knee to below-knee amputation,
which has benefits in energy expenditure, cardiovascular strain, and independence .
[27]

The beneficence argument for VCA of the extremity is further strengthened when the psychosocial
components of quality of life are also considered. Improvement in motor skills allows recipients to resume
their previous jobs, perform activities of daily living, and have a normal social life [28,29] . VCA also offers the
benefit of aesthetic restoration of body image that exceeds what can be achieved with prosthetics, salvage
procedures, and replantation. An important and increasingly recognized consequence of severe
disfigurements, such as limb loss, is that of “social death” - a construct constituting social isolation,
loneliness, ostracism, loss of personhood, altered role and identity, and personal harm - which has been
associated with physical pain and increased risk of mortality [30-33] . VCA carries the potential for the
treatment of social death - admittedly more applicable to upper versus lower extremity amputees, as the
former is more visible - that cannot be attained through alternatives. In fact, both functional and
psychosocial outcomes following hand transplantation have been shown to be superior to those associated
with the use of alternatives after limb amputation [34-37] . At up to 18 years post-transplantation, patients have
shown decreasing disability with excellent and improving outcomes per appearance, sensibility, mobility,
psychological and social acceptance, daily activities and work status, and patient satisfaction and general
[38]
well-being . Similar observations can likely be anticipated for patients after lower extremity
transplantation. By centering perspective around the whole person, VCA has been proposed as “lifesaving”
in recent literature [30,33] . This thereby negates the argument against the procedure as only life-enhancing and
demonstrates how VCA of the extremity can promote the best interests of the patient on multiple
dimensions.

Risks
While the potential benefits of VCA of the extremity are evident, there are substantial risks. First,
postoperative complications are an inherent risk for any extensive surgical procedure. Reported
complications for hand transplantation have included postoperative vessel thromboses, skin necrosis,
ischemic reperfusion injury, surgical site infections, pneumonia, sepsis, and acute limb loss [38-40] . Similar
complications would be expected for procedures involving the lower extremity, but the larger operative area
carries a greater risk for considerable blood loss - especially for proximal or bilateral transplants - than for
upper extremity VCA.

The primary concern surrounding VCA is recipients’ susceptibility to allograft rejection and a requirement
for long-term immunosuppression. Almost all hand transplant recipients experience at least one episode of
acute rejection within the first posttransplant year, and additional episodes beyond this point are not
rare [29,38,41] . Chronic rejection is an emerging threat that has been reported in nine cases to date, with graft