Immediate Enhancement of Nerve Function Using a Novel Axonal Fusion Device After Neurotmesis.

BACKGROUND: The management of peripheral nerve injuries remains a large challenge for plastic surgeons. With the inability to fuse axonal endings, results after microsurgical nerve repair have been inconsistent. Our current nerve repair strategies rely upon the slow and lengthy process of axonal regeneration (~1 mm/d). Polyethylene glycol (PEG) has been investigated as a potential axonal fusion agent; however, the percentage of axonal fusion has been inconsistent. The purpose of this study was to identify a PEG delivery device to standardize outcomes after attempted axonal fusion with PEG. MATERIALS AND METHODS: We used a rat sciatic nerve injury model in which we completely transected and repaired the left sciatic nerve to evaluate the efficacy of PEG fusion over a span of 12 weeks. In addition, we evaluated the effectiveness of a delivery device's ability to optimize results after PEG fusion. RESULTS: We found that PEG rapidly (within minutes) restores axonal continuity as assessed by electrophysiology, fluorescent retrograde tracer, and diffusion tensor imaging. Immunohistochemical analysis shows that motor axon counts are significantly increased at 1 week, 4 weeks, and 12 weeks postoperatively in PEG-treated animals. Furthermore, PEG restored behavioral functions up to 50% compared with animals that received the criterion standard epineurial repair (control animals). CONCLUSIONS: The ability of PEG to rapidly restore nerve function after neurotmesis could have vast implications on the clinical management of traumatic injuries to peripheral nerves.

A novel therapy to promote axonal fusion in human digital nerves.

BACKGROUND: Peripheral nerve injury can have a devastating impact on our military and veteran population. Current strategies for peripheral nerve repair include techniques such as nerve tubes, nerve grafts, tissue matrices, and nerve growth guides to enhance the number of regenerating axons. Even with such advanced techniques, it takes months to regain function. In animal models, polyethylene glycol (PEG) therapy has shown to improve both physiologic and behavioral outcomes after nerve transection by fusion of a portion of the proximal axons to the distal axon stumps. The objective of this study was to show the efficacy of PEG fusion in humans and to retrospectively compare PEG fusion to standard nerve repair. METHODS: Patients with traumatic lacerations involving digital nerves were treated with PEG after standard microsurgical neurorrhaphy. Sensory assessment after injury was performed at 1 week, 2 weeks, 1 month, and 2 months using static two-point discrimination and Semmes-Weinstein monofilament testing. The Medical Research Council Classification (MRCC) for Sensory Recovery Scale was used to evaluate the level of injury. The PEG fusion group was compared to patient-matched controls whose data were retrospectively collected. RESULTS: Four PEG fusions were performed on four nerve transections in two patients. Polyethylene glycol therapy improves functional outcomes and speed of nerve recovery in clinical setting assessed by average MRCC score in week 1 (2.8 vs 1.0, p = 0.03). At 4 weeks, MRCC remained superior in the PEG fusion group (3.8 vs 1.3, p = 0.01). At 8 weeks, there was improvement in both groups with the PEG fusion cohort remaining statistically better (4.0 vs 1.7, p = 0.01). CONCLUSION: Polyethylene glycol fusion is a novel therapy for peripheral nerve repair with proven effectiveness in animal models. Clinical studies are still in early stages but have had encouraging results. Polyethylene glycol fusion is a potential revolutionary therapy in peripheral nerve repair but needs further investigation. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Adjuvant radiation therapy increases disease-free survival in stage IB Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. Adjuvant radiation increases survival in advanced stages, but efficacy in stage I disease is unknown. A retrospective review included all patients treated for stage I MCC during a 15-year period at Vanderbilt University Medical Center. Among 42 patients, 26 (62%) had a negative sentinel lymph node biopsy (stage IA) and 16 (38%) had clinically negative lymph nodes (stage IB) at the time of resection. Analysis using Cox regression revealed that higher stage and absence of adjuvant radiation are associated with increased disease recurrence (hazard ratio, 6.29; P=0.003 and hazard ratio, 4.69; P=0.013, respectively). Controlling for stage, radiation therapy significantly increased disease-free survival among patients with stage IB disease (P=0.0026) in a log-rank test comparing Kaplan-Meier curves. These findings support adjuvant radiation therapy in stage IB MCC patients with clinically negative lymph nodes who do not undergo sentinel lymph node biopsy.