Prospective Sensory Outcomes for Targeted Nipple Areola Complex Reinnervation (TNR) in Gender-Affirming Double Incision Mastectomy with Free Nipple Grafting.

OBJECTIVE: This study analyses the anatomy and sensory outcomes of targeted nipple areola complex reinnervation (TNR) in gender-affirming double incision mastectomy with free nipple grafting (FNG). BACKGROUND: TNR is a novel technique to preserve and reconstruct intercostal nerves (ICN) to improve postoperative sensation. There is little evidence on relevant anatomy and outcomes. METHODS: 25 patients were prospectively enrolled. Data included demographics, surgical technique, and axon/fascicle counts. Quantitative sensory evaluation using monofilaments and qualitative patient reported questionnaires were completed preoperatively, and at one, three, six, nine and twelve months postoperatively. RESULTS: 50 mastectomies were performed. Per mastectomy, the median number of ICN found and used was 2 (1-5). Axon and fascicle counts were not significantly different between ICN branches ( P >0.05). BMI ≥30 kg/m 2 and mastectomy weight ≥800 g were associated with significantly worse preoperative sensation ( P <0.05). Compared to preoperative values, NAC sensation was worse at 1 month ( P <0.01), comparable at 3 months ( P >0.05), and significantly better at 12 months ( P <0.05) postoperatively. Chest sensation was comparable to the preoperative measurements at 1 and 3 months ( P >0.05), and significantly better at 12 months ( P <0.05) postoperatively. NAC sensation was significantly better when direct coaptation was performed compared to use of allograft only ( P <0.05), and with direct coaptation of ≥2 branches compared to direct coaptation of a single branch ( P <0.05). All patients reported return of nipple and chest sensation at one year postoperatively and 88% reported return of some degree of erogenous sensation. CONCLUSION: TNR allows for restoration of NAC and chest sensation within 3 months postoperatively. Use of multiple ICN branches and direct coaptation led to the best sensory outcomes.

Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation.

INTRODUCTION: The biology of symptomatic neuromas is poorly understood, particularly the factors causing pain in human neuromas. Pain presence varies among and within individuals, with some having painful and nonpainful neuromas. To bridge these knowledge gaps, our group developed a protocol for assessing neuroma pain and collecting tissue for molecular analysis. This manuscript outlines our workflow and challenges and aims to inspire other centers to share their experiences with these tissues. METHODS: For every included patient and collected nerve or bone tissue specimens, we perform a detailed chart review and a multifaceted analysis of pain and pain perception immediately before surgery. We collect patient-reported outcome measures (PROMs) on pain, function, and mental well-being outcomes at preoperative assessment and at the 6-month follow-up postoperatively. Before surgery, the patient is assessed once again to obtain an immediate preoperative pain status and identify potential differences in pain intensity of different neuromas. Intraoperatively, specimens are obtained and their gross anatomical features are recorded, after which they are stored in paraformaldehyde or frozen for later sample analyses. Postoperatively, patients are contacted to obtain additional postoperative PROMs. RESULTS: A total of 220 specimens of nerve tissue have been successfully obtained from 83 limbs, comprising 95 specimens of neuromas and 125 specimens of nerves located proximal to the neuromas or from controls. CONCLUSIONS: Our approach outlines the methods combining specimen collection and examination, including both macroscopic and molecular biological features, with PROMs, encompassing physical and psychological aspects, along with clinical metadata obtained through clinical teams and chart review.

Social Deprivation is Associated with Increased Pain in Patients Presenting with Neuropathic Pain.

Background: Neuropathic pain following nerve injury can be debilitating and negatively impact quality of life. Targeted muscle reinnervation (TMR) is an efficacious technique for the management of neuropathic pain. However, this technique may be unequally available for many geographical locations. Therefore, the aim of this study was to evaluate the association between Area Deprivation Index (ADI) and preoperative pain in patients undergoing TMR for treatment of neuropathic pain. Methods: Patients who underwent TMR for neuropathic pain in the lower and upper extremities were prospectively enrolled at our tertiary care clinic. A chart review was conducted to obtain socioeconomic, surgery, and comorbidity parameters. Preoperative pain scores (0-10 pain score index), and the ADI, reflecting deprivation status on a 0-100 scale, were collected. Results: A total of 162 patients from 13 different states were included, of which 119 were amputees (74%). The median ADI was 25 (IQR: 16-41) and the median preoperative pain score was 6 (IQR: 5-8). A higher ADI was independently associated with higher preoperative pain. The time interval from nerve injury to TMR was not associated with ADI. Conclusions: Patients undergoing surgical treatment of neuropathic pain from more socially deprived settings have increased pain experience upon initial evaluation, despite having similar time from nerve injury or amputation to TMR. These findings highlight the importance of identifying patients presenting from socially deprived settings, as this may impact their physical and mental health along with their coping mechanisms, resulting in increased pain.

Three Useful Tips and Tricks for Intraoperative Nerve Stimulation.

Disposable handheld nerve stimulators are widely used in peripheral nerve surgery. Such devices stimulate a motor nerve or the motor component of a mixed nerve by applying electrical current to the proximal region, targeting the main nerve trunk. This stimulation then travels along the motor nerve, reaching the distal end to control the corresponding muscle(s). In this study, the authors demonstrate three useful tips and tricks for handheld nerve stimulation during targeted muscle reinnervation and peripheral nerve surgery. The three tips are (1) identification of proximal muscle contraction by retrograde electrical stimulation of a distal sensory nerve; (2) graded stimulation for identifying motor nerves within fibrotic scarred tissue beds or parallel to the major motor/mixed nerve of interest; and (3) proximal stimulation for validation of adequate post-targeted muscle reinnervation coaptation(s).

Heterotopic Ossification Is Associated with Painful Neuromas in Transtibial Amputees Undergoing Surgical Treatment of Symptomatic Neuromas.

BACKGROUND: A relationship between nerve and osseous regeneration has been described. During the surgical treatment of symptomatic neuroma in transtibial amputees, we have noticed that heterotopic ossification (HO) depicted on preoperative radiographs appears to be associated with the location of symptomatic neuromas in both the peroneal and tibial nerve distributions. METHODS: Data were collected for transtibial amputees who underwent surgical management of symptomatic neuroma and were prospectively enrolled from 2018 through 2023. Preoperative radiographs were assessed for the presence of HO located at the distal fibula and tibia. The presence of a peroneal and/or tibial neuroma was based on findings contained within the operative reports. Pain levels were measured on a numeric rating scale (0-10). RESULTS: Sixty-five limbs of 62 amputees were include. Peroneal neuroma and presence of fibular HO (P=0.001), and tibial neuroma and presence of tibial HO (P=0.038) demonstrated an association. The odds of having a symptomatic peroneal neuroma with fibular HO present are greater than the odds of a symptomatic peroneal neuroma when fibular HO is absent (OR 9.3; 95%CI [1.9-45.6], P=0.006). Pre-operative pain scores were significantly higher for all patients with HO (P<0.001), those with fibular HO (P<0.001), and those with tibial HO (P<0.001), compared to patients without HO. CONCLUSIONS: In patients with symptomatic neuromas, preoperative pain was worse when HO was present in the transtibial amputee's residual limb. Further research on the neuroma-HO-complex in symptomatic amputees is required. LEVEL OF EVIDENCE: Therapeutic Level IV.

Predictive Value of Preoperative Pain Sketches in Lower Extremity Amputees Undergoing Secondary Targeted Muscle Reinnervation for Treatment of Neuropathic Pain.

BACKGROUND: Targeted Muscle Reinnervation (TMR) is an effective surgical treatment for neuropathic pain in amputees. Qualitative descriptions of pain, depicted by pain sketches, could enhance the understanding of symptomatic improvement following surgery. Our aim is to assess whether pre-operative pain sketches, drawn by lower extremity (LE) amputees, can predict surgical outcomes following Secondary TMR surgery. STUDY DESIGN: Eligible patients were LE amputees who underwent Secondary TMR surgery between 2017 and 2023. Pain sketches and pain scores were prospectively collected both before and after surgery. The pain trajectory, as categorized by pre-operative pain sketches, was analyzed and assessed for improvement, defined as reaching the Minimal Clinically Important Difference (MCID). The transition into different pain sketches and the occurrence of phantom drawings were evaluated for their association with improvement. RESULTS: Fifty-eight patients were included, of which 18 (31.1%) depicted diffuse pain (DP), 26 (44.8%) depicted focal pain (FP), and 18 (24.1%) depicted radiating pain (RP) in their pre-operative sketch. FP sketches were associated with the lowest pre- and post-operative pain scores and most frequently developed into sketches indicating "no pain". RP sketches were associated with the least pain improvement, the lowest likelihood of achieving the MCID, and were more prevalent in patients with diabetes or depression. RP sketches were associated with phantom drawings; no other sketch types developed into RP sketches at the final follow-up. CONCLUSIONS: In LE amputees who underwent Secondary TMR, pre-operative pain sketches could serve as a helpful tool in predicting pain outcomes. RP sketches seemed to be associated with worse outcomes, and FP sketches with the most improvement.

A Relative Value Unit-Based Model for Targeted Nipple-Areola Complex Neurotization in Gender-Affirming Mastectomy.

Background: For transmasculine individuals, double-incision mastectomy with free nipple grafts is the most common procedure for gender-affirming chest masculinization. However, patients report decreased sensation postoperatively. Direct coaptation of intercostal nerves to the nipple-areolar complex (NAC) is an experimental technique that may preserve postoperative sensation, yet whether reimbursements and billing codes incentivize hospital systems and surgeons to offer this procedure lacks clarity. Methods: A retrospective cross-sectional analysis of fiscal year 2023 Medicare physician fee schedule values was performed for neurotization procedures employing Current Procedural Terminology codes specified by prior studies for neurotization of the NAC. Additionally, operative times for gender-affirming mastectomy at a single center were examined to compare efficiency between procedures with and without neurotization included. Results: A total of 29 encounters were included in the study, with 11 (37.9%) receiving neurotization. The mean operating time was 100.3 minutes (95% CI, 89.2-111.5) without neurotization and 154.2 minutes (95% CI, 139.9-168.4) with neurotization. In 2023, the average work relative value units (wRVUs) for neurotization procedures was 13.38. Efficiency for gender-affirming mastectomy was 0.23 wRVUs per minute without neurotization and 0.24 wRVUs per minute with neurotization, yielding a difference of 0.01 wRVUs per minute. Conclusions: Neurotization of the NAC during double-incision mastectomy with free nipple grafts is an experimental technique that may improve patient sensation after surgery. Current reimbursement policy appropriately values the additional operative time associated with neurotization relative to gender-affirming mastectomy alone.

Emerging Value of Osseointegration for Intuitive Prosthetic Control after Transhumeral Amputations: A Systematic Review.

Background: Upper extremity limb loss profoundly impacts a patient's quality of life and well-being and carries a significant societal cost. Although osseointegration allows the attachment of the prosthesis directly to the bone, it is a relatively recent development as an alternative to conventional socket prostheses. The objective of this review was to identify reports on osseointegrated prosthetic embodiment for transhumeral amputations and assess the implant systems used, postoperative outcomes, and complications. Methods: A systematic review following PRISMA and AMSTAR guidelines assessed functional outcomes, implant longevity and retention, activities of daily living, and complications associated with osseointegrated prostheses in transhumeral amputees. Results: The literature search yielded 794 articles, with eight of these articles (retrospective analyses and case series) meeting the inclusion criteria. Myoelectric systems equipped with Osseointegrated Prostheses for the Rehabilitation of Amputees implants have been commonly used as transhumeral osseointegration systems. The transhumeral osseointegrated prostheses offered considerable improvements in functional outcomes, with participants demonstrating enhanced range of motion and improved performance of activities compared with traditional socket-based prostheses. One study demonstrated the advantage of an osseointegrated implant as a bidirectional gateway for signal transmission, enabling intuitive control of a bionic hand. Conclusions: Osseointegrated prostheses hold the potential to significantly improve the quality of life for individuals with transhumeral amputations. Continued research and clinical expansion are expected to lead to the realization of enhanced efficacy and safety in this technique, accompanied by cost reductions over time as a result of improved efficiencies and advancements in device design.

The neuroma map: A systematic review of the anatomic distribution, etiologies, and surgical treatment of painful traumatic neuromas.

BACKGROUND: This study analyzed all reported cases of painful traumatic neuromas to better understand their anatomic distribution, etiologies, and surgical treatment. METHODS: PubMed, Embase, Cochrane, and Web of Science were searched in October 2023 for articles describing painful traumatic neuromas. RESULTS: In total, 414 articles reporting 5,562 neuromas were included and categorized into head/neck, trunk, upper extremity, lower extremity, and autonomic nerves. Distribution was as follows: Head/neck: 82 articles reported on 393 neuromas (93.2% iatrogenic) most frequently involving the lingual (44.3%), cervical plexus (14.9%), great auricular (8.5%), inferior/superior alveolar (8.3%), and occipital (7.2%) nerves. Trunk: 47 articles reported on 554 neuromas (92.9% iatrogenic) most commonly involving the intercostal (35.4%), genitofemoral (14.3%), and pudendal (12.9%) nerves. Upper extremity: 159 articles reported on 2079 neuromas (53.3% after amputation) most frequently involving the digital (46.9%), superficial radial (18.3%), and median (7.0%) nerves. Lower extremity: 128 articles reported on 2,531 neuromas (53.0% after amputation) most commonly involving the sural (17.9%), superficial peroneal (17.3%), and saphenous (16.0%) nerves. Autonomic nerves: 15 articles reported on 53 neuromas (100% iatrogenic) most frequently involving the biliary tract (73.9%) and vagus nerve (14.9%). Compared with the extremities, neuromas in the head/neck and trunk had significantly longer symptom duration before surgical treatment and the nerve end was significantly less frequently reconstructed after neuroma excision. CONCLUSION: Painful neuromas are predominantly reported in the extremities yet may occur throughout the body primarily after iatrogenic injury. Knowledge of their anatomic distribution from head to toe will encourage awareness to avoid injury and expedite diagnosis to prevent treatment delay.

Targeted muscle reinnervation at the time of amputation to prevent the development of neuropathic pain.

INTRODUCTION: Targeted muscle reinnervation (TMR) is an established modality for the surgical management of neuropathic pain. Although the preventive effect of primary (acute) TMR at the time of amputation has been demonstrated previously, it remains unclear how many and which patients benefit most. Therefore, this study investigated the proportion of patients achieving sustained pain prophylaxis following amputation, as well as factors associated with its efficacy. METHODS: Primary patients who underwent TMR with a minimum follow-up of 6 months between 2018 and 2023 were enrolled. Pain outcomes (numeric rating scale [NRS], 0-10), comorbidities, and surgical factors were collected from chart review. Patients achieving sustained pain prophylaxis (NRS of ≤3 for ≥3 months until final follow-up) were identified. Multilevel mixed-effect models and multivariable regression were used to visualize pain courses and identify associated factors. RESULTS: Seventy-five patients who underwent primary TMR were included (median follow-up: 2.0 years), of whom 57.3% achieved sustained pain prophylaxis whereas 26.7% reported pain disappearance. Distal amputation levels (p = 0.036), a lower Elixhauser Comorbidity Index (p = 0.001), and the absence of psychiatric comorbidities (p = 0.039) were associated with pain prophylaxis. CONCLUSION: This study demonstrates that more than half of all patients undergoing primary TMR achieved sustained pain prophylaxis, and approximately a quarter of patients achieved sustained pain disappearance. Several factors associated with these favorable outcomes are described. These results will aid in preoperative counseling, managing patient expectations, and selecting patients who may benefit most from primary TMR surgery. LEVEL OF EVIDENCE: IV - Therapeutic.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Targeted Nipple Reinnervation in Gender-affirming Mastectomy Using Autologous Nerve Graft.

Our team recently described targeted nipple reinnervation (TNR) during female-to-male gender-affirming mastectomy with free nipple grafting using either direct nerve coaptation or nerve allograft. The goals of TNR are to improve sensation (including erogenous sensation) and prevent numbness, paresthesias, chronic pain, and phantom sensation. Here, we describe our modified technique, which has evolved to use autologous intercostal nerve branches as donor nerves for reinnervation if direct nerve coaptation cannot be achieved. During TNR, the T3-T5 sensory branches are preserved and coapted to the repositioned nipple-areolar complex (NAC). In patients with donor nerves that were not adequate in length to allow for direct coaptation, autologous intercostal nerve branches were not used for coaptation (branches present along the chest wall that would otherwise be lost) or one of the T3-T5 branches were harvested. An end-to-end nerve repair between the autograft and donor nerves was done, and the donor nerve/autograft complex was coapted to the NAC. Targeted muscle reinnervation was performed after autograft harvest to prevent neuroma formation. TNR with intercostal nerve autograft is technically feasible in female-to-male gender-affirming mastectomy with free nipple grafting when direct coaptation is not possible. Chest reinnervation using autologous intercostal nerve branches as donor nerves is another option for reinnervation when the nerves are too short for direct coaptation. Because the collection of long-term data is ongoing, the effectiveness of NAC reinnervation using our technique will be described in a future publication.