Evaluating the Efficacy of Targeted Muscle Reinnervation (TMR) in Extremities Amputations of Pedis Squamous Cell Carcinoma: A Comprehensive Systematic Review, Meta-Analysis, and Meta-regression of Functional and Pain Outcomes

Introduction: Targeted Muscle Reinnervation (TMR) is an innovative surgical procedure initially designed for upper-limb amputations, which has shown growing potential for improving functional outcomes in below-knee amputees. TMR involves redirecting severed nerves from the amputated limb to nearby residual muscles, allowing these muscles to act as amplifiers for nerve signals, thereby improving prosthetic control. Recent advancements in TMR for below-knee amputations have highlighted its ability to reduce post-amputation complications, such as neuroma pain and phantom limb pain, while offering enhanced control over prosthetic limbs, thus improving mobility and quality of life. Methods Following PRISMA guidelines, a systematic review was conducted, sourcing studies up to May 2024 from PubMed, Cochrane Library, Scopus, Springer, and Epistemonikos. The analysis included randomized controlled trials (RCTs) and clinical trials. A meta-analysis was performed to assess phantom limb pain reduction, while study quality was evaluated using RoB 2.0, ROBINS-I, and ROBINS-E. Meta-regression examined the influence of variables such as age and sex on pain outcomes. Results Seven studies, including 363 patients, were analyzed. The meta-analysis showed that TMR significantly reduced phantom limb pain (MD: -1.74; 95% CI: -2.46 to -1.02; P<0.00001; I2=0%). However, the pooled risk ratio for phantom pain incidence (RR: 1.58; 95% CI: 0.61 to 4.11; P=0.35; I2=93%) indicated variable outcomes. Conclusion TMR significantly reduces phantom limb pain and improves prosthetic control, particularly for patients with SCC of the foot, ultimately enhancing their quality of life.