Updated algorithm for abdominal wall reconstruction.

Like any clinical regime, the algorithm for abdominal wall reconstruction requires routine updating as new options and techniques become available. Increased experience and understanding of new applications have allowed for improvements to the approach to complex abdominal wall defects. These improvements have increased efficiency and decreased risk, particularly in the area of staged reconstruction. Surgeons have continued to rely heavily on autologous reconstruction and local tissue advancement for long-term dynamic support. The current approach to abdominal wall reconstruction is based on understanding the literature, clinical experience, and the type of patients seen in practice. This article provides surgeons with the basic guidelines to follow when faced with complex abdominal wall defects and the tools necessary to solve these difficult problems in a responsible and reliable way.

The S.O.F.T. Cheek method: an approach to lower eyelid and midface rejuvenation.

Procedures to rejuvenate the lower eyelids and cheek are amongst the most common aesthetic surgeries performed today. Rejuvenation should be individualized based on the patients concerns, anatomic deformity, and medical condition. A balanced and natural clinical result often requires a combination of techniques designed to address each patient's individual pattern of aging, while maximizing patient safety. We present the S.O.F.T. Cheek method of analysis and treatment, which utilizes well-developed principles and techniques, to consistently maximize clinical results and patient satisfaction.

Delayed nerve repair is associated with diminished neuroenhancement by FK506.

OBJECTIVES/HYPOTHESIS: The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days. STUDY DESIGN: In vivo laboratory study. METHODS: Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14, 16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively. RESULTS: Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P <.05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P <.05). CONCLUSION: In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.

Pathophysiology of nerve injury.

The response to nerve injury is a complex and often poorly understood mechanism. An in-depth and current command of the relevant neuroanatomy, classifications systems, and responses to injury and regeneration are critical to current clinical success. Continued progress must be made in our current understanding of these varied physiologic mechanisms of neuro-regeneration if any significant progress in clinical treatments or outcome is to be expected in the future. Reconstructive surgeons have in many ways maximized the technical aspects of peripheral nerve repair. However, advances in functional recovery may be seen with improvements in sensory and motor rehabilitation after peripheral nerve surgery and with a combined understanding of the neurobiology and neurophysiology of nerve injury and regeneration.

Current approach to radial nerve paralysis.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify all potential points of radial nerve compression and other likely causes of radial nerve injury. 2. Accurately diagnose both surgical and nonsurgical causes of radial nerve paralysis. 3. Define a safe and effective approach to the surgical release and reconstruction of the radial nerve. Radial nerve paralysis, which can result from a complex humerus fracture, direct nerve trauma, compressive neuropathies, neuritis, or (rarely) from malignant tumor formation, has been reported throughout the literature, with some controversy regarding its diagnosis and management. The appropriate management of any radial nerve palsy depends primarily on an accurate determination of its cause, severity, duration, and level of involvement. The radial nerve can be injured as proximally as the brachial plexus or as distally as the posterior interosseous or radial sensory nerve. This article reviews the etiology, prognosis, and various treatments available for radial nerve paralysis. It also provides a new classification system and treatment algorithm to assist in the management of patients with radial nerve palsies, and it offers a simple, five-step approach to radial nerve release in the forearm.

Risks associated with "components separation" for closure of complex abdominal wall defects.

The reconstruction of complex abdominal wall defects can often pose a significant challenge to surgeons and their patients. Complex ventral hernias may result from large tumor resections, trauma from gunshot wounds, or infections following routine abdominal surgery. "Components separation" of the abdominal musculature uses advancement of local autologous tissue, when available, to close large ventral wall defects. The authors report on a retrospective chart review of 30 patients who underwent components separation for the closure of complex abdominal defects. The study group was 50 percent female, with a mean age of 45 years, body mass index of 33.2 kg/m2, and abdominal defect size of 240 cm2. On average, 20 percent of patients had preoperative wound infections, 30 percent had intraoperative bowel enterotomies, and 33 percent required prosthetic mesh for closure. Total surgery time averaged 4.8 hours, with a mean postoperative stay of 12.5 days and follow-up of 9.5 months. The recurrence rate was 10 percent; postoperative complications included midline ischemia, infection, and dehiscence occurring at rates of 20, 40, and 43 percent, respectively. This study provides a comprehensive review of the risks and complications associated with the treatment of complex ventral hernias and those associated with abdominal "components separation."

Dose-dependent effects of FK506 on neuroregeneration in a rat model.

This study explored the effects of different doses of FK506 on peripheral nerve regeneration, to determine whether neuroregeneration could be enhanced without the toxicity of systemic immunosuppression. In the first part of the study, subimmunosuppressive doses of FK506 were determined by examining skin allograft survival in a rat model. Full-thickness skin grafts (2 cm2) from Wistar rats were grafted to recipient Lewis rats. The procedure was performed for six groups (n = 6). The control group received no FK506, and the other five groups received daily doses of FK506 of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg. Animals that received 2.0 mg/kg FK506 per day exhibited complete skin graft take, whereas all other groups demonstrated complete rejection. After determination of the immunosuppressive dose of FK506, the neuroregenerative effects of different doses of FK506 were explored by assessing nerve regeneration in 80 rats after tibial nerve transection and repair. The control group received no FK506, whereas the other four groups were given daily doses of FK506 of 0.25, 0.5, 1.0, or 2.0 mg/kg. Rats were euthanized at three time points (25, 30, and 35 days), to fully investigate the effects of different FK506 dosing regimens on neuroregeneration. Histomorphometric analyses performed on postoperative days 30 and 35 demonstrated statistically significant improvements in neuroregeneration with subimmunosuppressive FK506 doses of 0.5 and 1.0 mg/kg per day. Therefore, the study demonstrated that neuroregeneration was enhanced at low doses of FK506 that were not sufficient to prevent skin allograft rejection.

The effects of rapamycin in murine peripheral nerve isografts and allografts.

The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.

The effects of cavernous nerve grafting following surgically induced loss of erectile function in a large-animal model.

BACKGROUND: Prostate cancer is the second most common cause of cancer deaths in men in the United States. Many patients experience partial or complete loss of erectile function following prostatectomy. The cavernous nerves can be reconstructed intraoperatively using sural nerve grafts in an attempt to restore erectile function. METHODS: In this study, multiple anatomical dissections and neurologic assessments were used to define the position and histologic parameters of the cavernous nerve in a canine model. The subsequent experimental design included three groups of adult mongrel dogs followed for an 8-month period. Group 1, the control group, underwent bilateral nerve ablation to substantiate surgically induced loss of erectile function. Group 2, the "sham" group, underwent exploration only. Group 3 underwent bilateral cavernous nerve ablation with bilateral sural nerve graft reconstruction. Erectile function was evaluated with indirect electrical nerve and manual penile stimulation preoperatively and 1, 2, 4, 6, and 8 months postoperatively. Direct nerve stimulation and histologic analysis was preformed at the first operation and at the time the animals were euthanized at 8 months. RESULTS: Bilateral cavernous nerve ablation resulted in a significant loss of erectile function for 8 months postoperatively in the control animals. The sham animals demonstrated preservation of erectile function immediately following exploration. The animals in the grafted group demonstrated a significant return of erectile function by 4 months compared with preoperative measurements and by 2 months compared with control animals. CONCLUSIONS: This study establishes the first large-animal model for surgically induced loss of erectile function with successful cavernous nerve graft reconstruction, and it provides the unique opportunity to explore the effects of changes to this model in the future.

Assessment of the immune response to dose of nerve allografts.

Nerve allotransplantation provides a limitless source of nerve graft material for the reconstruction of large neural defects. It does require systemic immunosuppression or induction of immune unresponsiveness to prevent allograft rejection. It is unknown whether a greater volume of nerve graft material will increase the risk of rejection or the need for more intensive immunosuppression. This study assessed the relationship between the quantity of nerve tissue transplanted and the magnitude of the resulting immune response. Forty female (BALB/c) mice were randomly assigned to two groups that received either nerve isografts (BALB/c) or nerve allografts (C57BL/6). Each group was then subdivided into two groups that received either one or 10 sciatic nerve graft inlays. Histological and immunological assessments were performed at 10 days after engraftment. Histologic analysis demonstrated greater cellular infiltration in the allograft than the isograft groups but no appreciable difference in infiltration related to quantity of transplanted nerve tissue. In vitro assessments of the immune response using mixed lymphocyte assays and limiting dilution analysis similarly demonstrated a robust immune response to allografts but no effect on quantity of transplanted nerve tissue. These data suggest that larger peripheral nerve allografts may not be subject to increased risk for rejection.

Analysis of the nerve branches to the orbicularis oculi muscle of the lower eyelid in fresh cadavers.

BACKGROUND: Scleral show or ectropion is a known complication of lower eyelid surgery. It is particularly problematic after lower eyelid blepharoplasty when the orbicularis oculi muscle is transected or after other procedures are performed that denervate the lower eyelid. The purpose of this study was to determine whether a dominant motor branch exists to the lower lid orbicularis oculi muscle, using anatomic dissection and histologic analysis. METHODS: Sixteen fresh facial cadaver halves were dissected using the operative microscope to identify and measure nerve branches. The nerves were then harvested, sectioned, and stained with toluidine blue dye for histomorphometric analysis. Nerves were categorized as either lateral or medial to a vertical line marked at the lateral edge of the limbus of the eye. RESULTS: Eighty-seven percent and 47 percent of cadaver halves had one and two nerve branches lateral to the limbus, respectively. Eighty percent and 47 percent of cadaver halves had one and two nerve branches medial to the lateral limbus, respectively. The nerve branches entered the inferior edge of the orbicularis oculi muscle between 0.88 cm (+/-0.36 cm) and 2.73 cm (+/-0.46 cm) from the lateral canthus. There was no correlation noted between fascicular counts and distance from the lateral canthus. CONCLUSIONS: Multiple motor nerves exist to the lower eyelid. Branches are found medial and lateral to the lateral limbus, and no nerve branch is dominant.

Effects of Schwann cells and donor antigen on long-nerve allograft regeneration.

Nerve allotransplantation has been used successfully in human subjects to restore function after traumatic nerve injury and avoid subsequent limb amputation. However, due to the morbidity associated with nonspecific immunosuppression, this reconstructive approach has been limited to patients with particularly severe nerve injuries. It would be desirable to broaden the indications for such procedures through development of less toxic antirejection therapies. A miniature swine model of nerve transplantation was used to investigate the effects of preoperative ultraviolet-B (UV-B)-irradiated donor alloantigen portal venous infusion and injection of cultured major histocompatibility complex (MHC)-matched Schwann cells into the nerve graft. The transplanted ulnar nerves were harvested at 20 weeks. Histomorphometry showed marked enhancement in nerve regeneration through allografts injected with Schwann cells. Serial mixed lymphocyte assays demonstrated suppression of the recipient immune response to the donor antigen after pretreatment, but no additional neuroregenerative effect of donor alloantigen pretreatment.

The position of crossing branches of the medial antebrachial cutaneous nerve during cubital tunnel surgery in humans.

The posterior branch of the medial antebrachial cutaneous nerve courses in proximity to the cubital tunnel and is particularly prone to injury during ulnar nerve release at the elbow. Inadvertent injury to medial antebrachial cutaneous nerve branches during surgery can result in the formation of painful neuromas that can be misdiagnosed as recurrent disease. It is important to understand the relevant anatomy of the medial antebrachial cutaneous nerve branches during cubital tunnel surgery to avoid significant postoperative morbidity. This prospective observational anatomic study examined the position of the posterior branch of the medial antebrachial cutaneous nerve in relationship to a standard approach to the cubital tunnel in a randomly selected group of 97 patients undergoing primary surgery over a 3-year period. Medial antebrachial cutaneous nerve branches were noted to cross at or proximal to the medial humeral epicondyle 61 percent of the time at an average proximal distance of 1.8 cm. Medial antebrachial cutaneous nerve branches were noted to cross distal to the medial humeral epicondyle 100 percent of the time at an average distal distance of 3.1 cm. Understanding the general position of crossing medial antebrachial cutaneous nerve branches during ulnar nerve release at the elbow may help to prevent iatrogenic injury to this cutaneous nerve.

Effects of tobacco smoke on recovery after nerve crush injury in rats.

The effects of tobacco smoke on nerve healing after crush injury was studied in a rat model. Thirty-six animals were randomized equally into smoke-exposed or nonsmoke-exposed groups. Two nerve crush injuries were performed on the right posterior tibial nerve of each animal at 4-week intervals to mimic a sustained or chronic nerve injury. Recovery of the two groups was assessed with walking track analysis and nerve histomorphometry. There was no difference in the rate of nerve recovery based on walking track analysis in the smoke-exposed animals compared with nonexposed animals. The study also failed to demonstrate any significant difference between the two groups as assessed by histomorphometric criteria.

Controlled release of nerve growth factor enhances sciatic nerve regeneration.

Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the mid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps.

Anti-CD40 ligand antibody permits regeneration through peripheral nerve allografts in a nonhuman primate model.

Systemic immunosuppression is typically required to prevent allograft rejection. Antibody-based therapies that induce immune unresponsiveness represent an appealing alternative to nonspecific immunosuppression, which is often associated with significant morbidity. In mice, successful prevention of nerve allograft rejection has been demonstrated through interference with the CD40/CD40 ligand interaction. This study investigated the effectiveness of anti-CD40 ligand monoclonal antibody as single-agent therapy in preventing rejection and supporting nerve regeneration across long nerve allografts in nonhuman primates. Twelve outbred cynomolgus macaques were arranged into six genetically mismatched pairs, with each animal receiving a 5-cm ulnar nerve allograft in the right arm and a 5-cm autograft in the left arm. Mixed lymphocyte reaction assays were used to assess resulting immune unresponsiveness. Treated animals (n = 10) received anti-CD40 ligand monoclonal antibody 10 mg/kg one time, locally applied, and 20 mg/kg systemically on postoperative days 0, 1, 3, 10, 18, and 28, and then monthly. Untreated animals (n = 2) served as the untreated controls. At 4 or 6 months after transplantation, nerves were harvested for histological analysis. Four treated animals underwent an additional challenge after cessation of anti-CD40 ligand monoclonal antibody therapy and nerve graft harvests. Autogenous and allogeneic skin and nerve inlay grafting was performed to assess the permanence of immune unresponsiveness induced by anti-CD40 ligand monoclonal antibody. Animals that received anti-CD40 ligand monoclonal antibody demonstrated robust regeneration across nerve allografts, similar to that seen in the autograft control in the contralateral arm. The histomorphometric analysis of allografts in the untreated animals demonstrated significantly worse measurements compared with their matched autograft controls. Animals that received anti-CD40 ligand monoclonal antibody with concomitant skin allografts had virtually no evidence of nerve regeneration through allografts. Allogeneic skin and nerve allografts applied 2 to 12 months after withdrawal of anti-CD40 ligand monoclonal antibody therapy were consistently rejected. This study demonstrates that anti-CD40 ligand monoclonal antibody prevents rejection and allows regeneration of peripheral nerve allografts in nonhuman primates. The effect of anti-CD40 ligand monoclonal antibody appears to be transient, however, with restoration of immunocompetence shortly after withdrawal of therapy.