When considering the merits of hand transplantation, the ability to successfully use a prosthesis must first be considered. There are many options for a prosthesis in patients with a midforearm amputation. Patients with a transmetacarpal stump are usually able to use their wrists well to perform many activities and the additional values of a prosthesis can be limited. Amputations at the radiocarpal level preserve length well but have very little function without a prosthetic; yet fitting a useful prosthesis at this level can be difficult. A transhumeral amputation can work well with a prosthesis, but the success of this is dependent on shoulder mobility, and overall function is likely to be poorer than a midforearm prosthesis.1
Transplantation is considered for traumatic amputations (as opposed to congenital absences) with strict inclusion criteria. The main indication for hand transplantation is a bilateral upper or quadrimembral amputee, or an amputee who has lost their dominant upper limb. Indications for single upper limb amputations are less clear-cut. This patient has retained his dominant upper limb so is very unlikely to warrant the risks associated with the procedure and lifelong immunosuppression. Other criteria include older than 18 years, a good state of general health, and an adequate period of using a prosthesis (which can be arranged after the initial assessment if not already undertaken). He would therefore not be excluded on these grounds. Each case must be judged on its own merits and due thought also given to the quality of the remaining tissues at the stump, which is influenced by the mechanism of injury. Level of injury is important, as removal of a failed transplanted limb should ideally not leave the patient in a worse functional position than when they started; this is difficult to avoid in a transmetacarpal amputation.1–3
3. Hollenbeck ST, Erdmann D, Levin LS. Current indications for hand and face allotransplantation. Transplant Proc 2009;41(2):495–498 Hepatitis A is an acute, self-limiting viral infection that does not lead to chronic infection. Although there may be liver damage if the initial infection is severe, this can be screened for during assessment for transplant. Active hepatitis infection or HIV represent contraindications to transplant as do a current diagnosis of cancer, high risk of cancer recurrence (such as shortly after mastectomy and radiotherapy), pregnancy, immunologic dysfunction, and hypercoagulable states. Hand transplantation is generally contraindicated in the management of congenital limb anomalies. In congenital limb absence, the patient will have no prior experience of a functioning limb at the defect site and will have lifelong learned behavior patterns and cortical representation that are based on the limb deficit being their normal state. Also, in the trauma setting there are predictable recipient structures to unite, which is often not the case in congenital anomalies.1–3
Assessment of the physical characteristics of the limb is critical in achieving a good outcome following hand transplant. This affects the functional, cosmetic, and psychological outcome, and also affects practical steps such as completing osteosynthesis of the radius and ulna in the forearm. It is the responsibility of the transplant team to optimize this match and therefore they will be closely involved in selection. Skin tone, hair density, and overall physical match with the recipient are important, so even when there may be a suitable donor match in terms of blood grouping, etc., transplant may be stopped based on physical criteria. While correct ABO typing and crossmatching are key to a successful transplant, the surgical team does not need to meet the donor to gather this information. During immunological screening, a positive crossmatch is a major problem as it means that the recipient has preformed antibodies to the donor tissue and will likely undergo a hyperacute rejection. In many transplant programs, contact with the donor family is through the specialist in organ donation who is seeking consent for donation of all (or selected) organs. The upper limb transplant team will usually have made arrangements for the additional consent elements to be included in this process (such as pointing out that the donated limbs will be visible, and that media attention is not always avoidable).1–3
This method of removing the donor limb is swift, minimizing the impact on solid-organ retrieval. It also preserves all the required distal tissues with excess length to allow accurate preparation in the recipient operating room. A two-team approach is preferred within the recipient operating room area, so the ischemic time is kept to a minimum. The teams must coordinate closely to ensure matched osteotomies and clear tagging of important structures at an appropriate length. The sequence of reconstruction varies according to amputation level and tissue type. The urgency to revascularize depends on composite tissue types included, with greater urgency in grafts having a significant muscle component (in more proximal transplants). For a distal forearm transplantation, a typical sequence would be bony fixation, extensor tendons (set to full extension with the wrist flexed), dorsal veins, nerves, arteries, and flexor tendons. This ensures that the dorsal structures are all repaired first prior to supinating for volar structure repairs; therefore, the limb does not require repeated manipulation back and forth during revascularization. At this level, a grouped fascicular nerve repair technique is recommended over an epineural repair where possible to facilitate better matching of predominantly motor and sensory bundles.1–3
Patients taking immunosuppressive drugs for transplant surgery may develop hypertension or hyperglycemia as a consequence, often requiring medications to address this.1 Gastroprotective medication may also be required as a result of prolonged corticosteroid use. Metabolic complications reported following hand transplant in a 28-patient review included hyperglycemia in 13 patients (46.42%), hypertension in 7 patients (25%), and hyperlipidemia in 4 patients (14.28%).2 Preparation for this is an important component of the preoperative counseling and consent process. While metabolic complications are a common side effect of immunosuppressive regimens, these changes are usually reversed as immunosuppressive medication doses are reduced or stopped. Induction immunotherapy is performed before surgery to prevent acute rejection. Lymphocyte depleting agents are used and include antithymocyte globulin and alemtuzumab. Tacrolimus (Prograf) is also used in the induction phase; however, it is a calcineurin inhibitor that reduces lymphocyte activation and not a depleting agent. Tacrolimus also appears to have an additional secondary beneficial effect on nerve recovery/regeneration.3 The most common maintenance regimen is triple therapy with tacrolimus, mycophenolate mofetil (MMF), and corticosteroids. Many protocols attempt to reduce tacrolimus and it may be replaced by rapamycin. MMF is a common component of both induction and maintenance regimens, having a role in B- and T-lymphocyte suppression. It is considered to be much less hepatotoxic than its predecessors: cyclophosphamide and azathioprine.2–5
Vascularized composite allografts contain a number of different tissue types such as skin, bone, muscle, and nerve within a single graft. Of these tissue components, skin is the most antigenic and, as a result, direct inspection is important to identify acute rejection. This will manifest as erythematous macules, diffuse redness, or asymptomatic papules. For this reason, patients should be seen in clinic on a regular basis after transplant and must be educated in reporting potential signs of rejection.1–5
It is reasonable to expect a good sensory recovery after hand transplant, with more than 90% reported rates of return for tactile, pain, and temperature sensation. While extrinsic motor function is expected in all cases, the rate of intrinsic recovery is less predictable. A midforearm transplant is more likely to produce a good result than a more proximal transplant; there is a shorter distance for nerve recovery to reinnervate distal muscles, there is a functioning elbow, and there is the possibility of strong Pulvertaft tendon weaves for uniting the extrinsic motor units (rather than muscle belly repairs). Peak recovery is not at 1 year, as recovery is expected to continue for several years. The DASH score is a well-regarded scoring system used for upper limb function. However, it is not specific to hand transplantation. A hand transplantation score has been developed (HTSS) and this has six key areas: appearance, sensibility, movement, psychological and social acceptance, activities of daily living, and patient satisfaction.1–5
In spite of the rigorous medical regimen, the side effects from medications, and the intrusive therapy and monitoring schedule, more than 75% of patients have a subjective improvement in quality of life after a hand transplant. Most patients perform activities of daily living independently and some have returned to full employment. The risk of metabolic complications is approximately 70%. The risk of hyperglycemia-induced problems secondary to immunotherapy is around 45%. Acute rejection has been a consistent problem after limb transplant, with 85% incidence within the first year. These episodes are, however, usually treatable with immunotherapy modification. The risk of opportunistic infection is high because of immunosuppression. This is estimated to be approximately 60 to 65%. Infections include cytomegalovirus, herpes, and bacterial subtypes. Appropriate prophylaxis is required, particularly in the first 6 to 12 months. The risk of graft loss is low across all series of vascularized transplant, although the Chinese series on limb transplant reported losses over 40% because of poor postoperative compliance with medical therapy.1
Vascularized composite allograft rejection is graded according to the Banff classification,1 which is based on the histological appearances of a 4-mm punch biopsy specimen. The grades of rejection range from 0 to 4 based on evidence of the extent and severity of inflammatory change and the presence or absence of cell necrosis.
The first-line agent in an acute rejection episode is a high-dose corticosteroid (prednisolone/hydrocortisone), while ensuring that tacrolimus or MMF doses are optimized. Second-line agents include high-dose tacrolimus, monoclonal antibodies, and sirolimus.1