Intraoperative Sterilization of Nerve Grafts for Reimplantation in Tumor Surgery: An Interesting Technique with Many Open Questions

We thank the authors for this interesting study demonstrating the effects and technical feasibility of extracorporeal irradiation and liquid nitrogen freezing on nerve recovery in an animal model. [1]

The general concept of graft sterilization has already been used successfully for the reconstruction of bone defects, [2] however this is the first study to show the effects of sterilization and reimplantation on nerve recovery. The authors felt, that the inclusion of (tumor) contaminated nerve was not warranted, as the sterilization methods are already proven in clinical practise. In this regard we strongly disagree. As is, this study only shows the effects on nerves, which have had no other external stressors (except for the applied sterilization method). In cases in which this technique might be useful, i.e. if the tumor encases the nerve, there may already be additional structural damage to the nerve like in compression neuropathies [3]. There is no data on how this may influence regeneration after sterilization. Furthermore, although rare, there may be direct invasion of the nerve [4] which may further change nerve structure and influence regeneration after reimplantation. These effects of that cannot just be deduced from previous studies, that did not take into account all confounding factors.

In cases in which the tumor only touches the nerve, no sterilization is necessary as research from our center [5,6] as well as others [7] has shown that a close margin resection (i.e. epineural dissection) can be done without compromising oncological safety. Furthermore, we would recommend not opening the tumor ex situ in the OR, especially in close margin resections (which we routinely perform with excellent oncological results and find desirable to preserve best possible patient quality of life) as this may make it more difficult (perhaps even impossible) for the examining pathologists to confirm R0-resection, especially if they are not very experienced with sarcoma. Thus, in a clinical setting, we would only approach the authors’ technique with great caution.

We agree with the authors, that the use of a homotopic autograft would be desirable, as this would most closely reconstruct the fascicular structure (and possible branching pattern) of the nerve. The study by Strasberg et al. [8] (which the authors quoted regarding this) showed that heterotopic (not homotopic) cable autografting was superior to unprocessed fresh as well as cold preserved (5 °C storage) otherwise unprocessed allograft. This is expected as the immunogenic cells (and in case of sterilization the immunogenic protein complexes) are left intact and a host vs. graft immune response will obviously occur to some degree.

Furthermore, although interesting from an experimental point of view, it is unknown, if a sterilized homotopic autograft (which has possibly been structurally damaged by the tumor, too) would be able to provide better functional clinical outcomes as compared to the use of a heterotopic autograft (e.g. saphenous nerve) or commercially available allograft.

Depending on the nerve which has to be resected, it should be noted that the resulting sensory defect might be tolerable to the patient and the resulting motor defect might be better reconstructed by a tendon transfer [9] or a distal nerve transfer [10], especially if the distance to the muscle is too long for successful reinnervation.

The only way to clarify the actual outcome would be clinical studies. However before that, we think it is imperative, that it is elucidated (in experimental studies) which actually recreate the proposed typical setting (including the tumor) if the technique is actually comparable or superior to heterotopic autologous nerve grafts or processed, decellularized allograft.

Disclosure statement

The authors have no conflict of interest to report.