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Page 2 of 17 Toyoda et al. Plast Aesthet Res 2022;9:17 https://dx.doi.org/10.20517/2347-9264.2021.118

INTRODUCTION
Extremity amputation is one of the oldest procedures known to man, with archeological records suggesting
[1]
purposeful amputations as far back as 45,000 years since Neolithic times . The word “amputation” can
trace its origin to the Latin term “amputatio” meaning “to cut around” . Amputation continues to be
[1]
prevalent in the present day, with approximately 1.6 million people with major limb amputations in the
United States in 2005 and 185,000 major limb amputations every year . By 2050, the prevalence is
[2,3]
estimated to be as large as 3.6 million, given that the most common causes for amputation, especially in the
[1,3]
lower extremity, are diabetes and peripheral vascular disease, which continue to uptrend . Nontraumatic
lower extremity amputation is estimated at only 3/10,000 among the healthy population in 2010, but as high
[4]
as 28.4-46.2/10,000 among diabetics . Unsurprisingly, significant healthcare costs are associated with these
patients. The lifetime all-cause direct cost for lower extremity amputation was estimated to be $35.8 billion
[4]
for the country . No appropriate literature on the indirect or total cost of amputation currently exists, but it
is estimated to be significant as studies have found that after a major lower extremity amputation, up to
[4]
53.9% of patients were still nonambulatory at 6-month follow-up after the operation . Another
retrospective chart review of 206 patients who underwent major lower extremity amputation demonstrated
a one-year postamputation ambulatory rate of 46.1% . Furthermore, nonambulatory rates were higher in
[5]
those with higher BMI, which portend a poor future as the United States population suffers from increasing
rates of obesity . Lower extremity amputation is therefore not only a serious problem for individual
[5]
patients, but a large - and only increasing - burden on the United States healthcare system. We herein aim
to discuss post-amputation outcomes, epidemiology of chronic, post-amputation pain, and current
treatments including total muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI)
at the forefront of multidisciplinary treatment of lower extremity amputees.

Outcomes of amputation
Functional equivalence of lower extremity amputation compared to limb salvage was demonstrated in the
[6]
seminal Lower Extremity Amputation Prevention (LEAP) study . This was a multicenter, prospective,
observational study of 569 severe lower extremity injuries who received either amputation or
reconstruction . After two years of follow-up, the functional outcome of amputation and reconstruction as
[6]
[6]
measured by the Sickness Impact Profile was not significantly different . Rather, predictors of poor
outcome were more correlated with intrinsic patient factors such as education level, ethnicity, insurance
status, and social support . Amputation vs. salvage has been a difficult decision tree branching point even
[6]
for institutions well versed in critical limb injury. Ultimately, Black et al. offer some general consensus, but
[7]
concluded that many patient-specific factors, as well as injury factors, must be considered prior to decide
whether to amputate or salvage. Amputation is therefore not equivalent to failure to salvage, but a viable
alternative reconstructive option with likely functional equivalence in the appropriate patient population.

In evaluating functionality after amputation, Suckow et al. performed four focus groups in twenty-six
[8]
patients who had lower extremity amputations from critical limb ischemia. Quality of life was determined
mainly by impaired mobility (65%), pain (60%), progression of disease in the remaining limb (55%), and
depression/frustration (54%). Sixty-two percent had multiple prior revascularization procedures. Areas of
improvement included peer support (88%), extensive rehab/prosthetist involvement (71%), earlier mention
of amputation as a possible outcome (54%), and early discontinuation of narcotics (54%). Physician-
controlled factors such as the timing of amputation, informed decision-making, and postamputation
[8]
support, play an important role . For amputees, the function of their shortened limb correlates closely with
prosthetic use . These results have also been corroborated in the LIMB-Q, a patient-reported outcome
[9]
instrument in which numerous themes were extracted from direct interviews with patients who suffered
high-energy lower extremity trauma . Themes such as physical ability, psychological, and prosthesis were
[10]
important to patients’ daily quality of life . As expected, a long-term study of patients over 20 years after
[10]