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Page 2 of 11 Marsden et al. Plast Aesthet Res 2019;6:24 I http://dx.doi.org/10.20517/2347-9264.2019.14

over the optimum timing of radiotherapy in the management of extremity STS. Preoperative radiotherapy
is associated with better overall survival but higher wound complications compared to postoperative
[7]
[6]
radiation . The most important factor in obtaining local control is wide surgical excision margins ,
which often involves the loss of major musculotendinous and neurovascular units in the extremities. These
complex defects are further complicated by the issues of radiation related wound complications, which has
led to the popularisation of free and pedicled flaps to reconstruct extremity STS defects. The main benefits
of importing vascularised tissue in the form of free/pedicled flaps is to fill dead space, attain wound closure,
protect important neurovascular structures, and improve wound healing . Despite these advances in
[8,9]
reconstruction, a large proportion of patients will rely on splints and orthotics to aid activities of daily
living, and the overall function remains poor.

More recently, there has been a paradigm shift in the goals of STS reconstruction, to a more innovative,
functional approach, whereby the aim is to replace missing elements (e.g., skin, bone, tendon, muscle and
neurovascular structures), restore functional muscle units and critical sensory pathways and provide soft
tissue coverage in one procedure [10-13] . The aim of this paper is to review current innovative techniques of
functional limb reconstruction in the irradiated setting, and present our experience in this challenging
field.

PERIPHERAL NERVE RECONSTRUCTION
Wide excision of composite tissue in sarcoma surgery may lead to segmental loss of critical sensory and
motor nerves, with devastating functional loss. There are several techniques described for reconstructing
nerve gaps, whereby direct epineural repair is not an option, including autologous nerve grafts, allografts
and nerve conduits. The difficulty in the post radiation setting is the poor vascularity of the wound beds,
leading to generally poor results with conventional techniques.

Although the results of functional recovery after nerve repair and nerve grafts had historically been
attributed to irreversible muscle atrophy and the replacement of muscle with fat over time, research has
demonstrated that this is not the sole factor responsible and progressive Schwann cells denervation, nerve
[14]
ischaemia, intraneural fibrosis and chronic axotomy also play significant roles . The vascularised nerve
[15]
graft (VNG), described by Taylor and Ham , involves the transfer of a donor nerve along with its vascular
pedicle. Transfer of a vascularised nerve graft avoids the initial period of nerve ischaemia and reduces
central necrosis and intraneural fibrosis seen particularly in medium- to large-sized non-vascularised
[16]
grafts . It is generally believed that VNGs perform better for longer gaps, larger diameter nerves and in
the setting of poorly vascularised or scarred beds, however high-quality evidence is lacking. Improved
nerve regeneration has been demonstrated with VNGs over standard nerve grafts in animal models in the
setting of poorly vascularised beds [17,18] . One of the suggested indications for the use of vascularised nerve
grafts is the poorly vascularised and scarred bed, such as in the setting of prior radiotherapy, whereby
success with standard nerve grafts is generally poor; however, there is not yet firm clinical evidence for
this [19,20] .

As a general rule, there is a 50% loss of axons at each nerve coaptation site. Therefore, with primary nerve
repair, approximately 50% of the original axons will successfully regenerate across the repair. With nerve
grafts, because of two coaptation sites, only around 25% of axons will regenerate successfully across the
distant coaptation, and there may be additional axonal loss depending on the distance to the distal target,
due to the effects of chronic axotomy and muscle fibrosis [16,21] . For this reason, nerve transfers, requiring a
single coaptation, are favoured over nerve grafts when possible, and nerves with higher axonal input are
favoured, to maximise axonal regeneration distally. Nerve transfer involves the coaptation of an expendable
healthy donor nerve to a denervated or cut nerve, with the aim of maximising functional recovery with