Hand Transplantation Treatment & Management
- Author: Bardia Amirlak, MD; Chief Editor: Ron Shapiro, MD more...
Selected immunosuppressants prescribed for hand transplant patients include medications used during the induction and maintenance phases.
Immunosuppressive medications used for the induction phase include a calcineurin inhibitor such as tacrolimus (FK506), an antimetabolite such as mycophenolate mofetil (MMF), a monoclonal antibody such as alemtuzumab, and a steroid such as methylprednisone.
Maintenance medications consist of steroids, antimetabolites, and calcineurin inhibitors in much lower doses than those used in the induction phase. More recently, Campath (alemtuzumab; Genzyme Oncology, Cambridge, Mass) has been used for induction, followed by a steroid-free regimen. This steroid-free maintenance therapy has shown promising results in other organ transplantation settings.
Specific dosing information is out of the scope of this article, since protocols in CTA vary among centers within the United States as well as around the world. The differences have been in the induction agents used (antithrombocyte globulin [ATG], basiliximab, Campath-1H) as well as in maintenance drugs (number of drugs, dosages). Most centers currently rely on triple drug combination therapy as used conventionally in solid organ transplants (FK506 + MMF + steroids). Some centers have steroid avoidance protocols in place, with other centers attempting CTA on tacrolimus monotherapy.
Arrangements such as charter flights or other means of rapid transport need to be set up in advance so that little time is wasted to transport the recipient to the designated center when a donor becomes available. All the appropriate psychiatric and social screening of the recipient needs to be completed before surgery. Appropriate laboratory studies, including complete blood count, basic metabolic profile coagulation profile, and ABO antibody screening, need to be re-obtained just prior to the surgery. Preoperative immunosuppression needs to be regulated as described above. Regional axillary nerve block can be used to minimize the postoperative pain. An axillary block also has the theoretical advantage of increasing the blood flow to the donor hand by vasodilatation effects on the peripheral vessels of the extremity.
Prior to transplantation, the appropriate tests for the donor limb need to be completed, as described in the previous sections.
In addition to immunosuppressive medication, the transplant center’s pharmacy needs to be equipped with all the appropriate medications for a major surgery, including antibiotics, antihistamines, narcotics, analgesics, gastrointestinal prophylaxis medications, and laxatives. Aspirin, as well as low-molecular-weight dextran with heparin, may be required for intraoperative and postoperative anticoagulation.
Limb retrieval begins with a sterile technique, and a tourniquet is placed above the elbow. The elbow is then disarticulated, after which the tourniquet is left in place to prevent prospective blood loss. To facilitate the closure time, staples should be used to close the incision. The harvested extremity is covered with moist gauze, and the vessels are cannulated and irrigated with University of Wisconsin solution (ViaSpan, Dupont Merck Pharmaceuticals, Wilmington, Del) at 4°C, which increases the duration of allowable ischemia (see image below). The limb should then be packaged, stored at the cooler, and prepared for transport to the recipient hospital.
At the recipient hospital, the arm is removed from the cooler and placed on the preparation table for dissection, typically in the same room as the recipient. The University of Wisconsin solution is flushed out of the donor part using chilled Ringer lactate solution.
The main hand transplant surgeon and assistant hand transplant surgeon (who helps in the dissection of the donor limb) are also assisted by 1 scrub nurse per extremity, 2 circulators per room, and at least 1 anesthesiologist. For bilateral hand transplantation, more personnel and equipment are needed. In addition to the recipient extremity and donor limb, both legs should be shaved and prepped to prepare for a possible tendon graft if needed.
Arrangements need to be made for the donor to be immediately fashioned with a life-like prosthesis in case an open casket ceremony is to be held after death.
Transplantation - technical details
Technical details of the surgery are generally similar to hand replantation. The donor and recipient limbs are prepared simultaneously on two different tables, preferably in the same room for better communication between the 2 teams (see image below).
For preparation of the donor limb after flushing out the University of Wisconsin solution, the excess skin and bone are removed. The tendons, arteries, veins, and nerves are subsequently identified. Measurements are taken of the radius and ulna, and the 2 bones are shortened appropriately.
For preparation of the recipient limb, the tendons, nerves, and vessels are dissected and identified (see image below).
The radius and ulna are cut to match the donor bones appropriately. Following bone fixation with metal plates (see image below), the vessels, nerves and tendons are connected.
A powerful microscope is used for attaching the nerves and vessels. If the recipient tendons are atrophic, modification such as tendon transfers or mass connection of the recipient tendons to donor tendons is considered. Tendon graft from opposite extremity or the feet may become necessary. Split-thickness skin grafts may become necessary for adequate coverage. Finally, the hand and arm are placed in a long-arm splint for immediate recovery, until fitted with the proper dynamic splint.
Upon transfer to a specialized postoperative care unit, the circulatory status of the transplant limb is assessed hourly by nursing staff. Blood flow to the transplant versus the unaffected limb is assessed with continuous pulse oximeter monitoring. A skin temperature monitoring device is used to assess the surface skin temperature of the transplanted hand compared with the unaffected extremity. Temperature readings should be at least 30ºC. The physician responsible for postoperative care should be immediately informed of any decreases in skin temperature or change in circulatory status.
Furthermore, the temperature in the patient's room should be maintained at 75ºF (24ºC). The patient is not allowed to consume caffeine, and smoking is strictly prohibited because of the vasoconstrictive affects of nicotine. The family is instructed to avoid smoking before visiting the patient. Pain control, nutrition, activity level, bowel and bladder function, and anti-embolic measures are continuously assessed by nursing staff throughout the patient’s hospital stay.
Postoperatively, electrical muscle stimulation may improve tendon gliding; therefore, encore electrodes should be placed along the median and ulnar nerves (above the transplant), along with a transcutaneous electrical nerve stimulator. The patient should receive physical and occupational therapy daily for at least the first postoperative week. Exercise guidelines should be based on the use of 4-6–strand tendon repair techniques.
The physical therapists should be capable of both static and dynamic splinting, including a proximal interphalangeal crane outrigger and a cast outrigger with static metacarpophalangeal flexion and dynamic thumb interphalangeal extension, which are all used in the early postoperative time. The crane outrigger should block metacarpal joints in flexion while allowing active flexion and dynamic interphalangeal extension (see image below).
This method protects healing while allowing gentle range of motion, thus limiting the formation of adhesions.[15, 16] Judging by the world experience in hand transplantation, this method appears to have the same superior results as seen when using this method in hand replantation. A hand-based anticlaw splint can be used with the outrigger as needed after 3 weeks. Compression gloves may be used for edema.
Immunosuppression is induced by a specific medication regimen and is monitored by the transplant physician and transplant coordinator. The coordinator visits the patient daily while in the hospital and is responsible for educating the patient and family on medications, activity restrictions and recommendations, environmental considerations, and necessary changes in activities of daily living in order to accommodate the healing and recovery of the transplanted limb. Because of the immunosuppressed status of the patient, the nurse overseeing the inpatient postoperative care should try to coordinate any visit by the necessary personnel and family members to minimize traffic in the patient’s room.
Posttransplant blood samples need to be drawn at regular intervals to screen for the development of antidonor antibodies. Ideally, serum is drawn concurrent with obtaining biopsies to facilitate correlation of histology with systemic markers of immunologic activation.
Biopsies should be performed regularly for suspected rejection or infection. Microbiological support services, rapid therapeutic drug level monitoring, and general hematologic and chemical studies relevant to the needs of these patients are necessary.
After transplant, body image and identity issues may need to be addressed as the patient gets used to seeing and using the new hand on his or her own. The postoperative psychotherapy should be enhanced or reduced in accordance with the patient's history of compliance with health care needs, as determined by the social worker and psychiatrist preoperatively. The patient's perception of composite tissue allotransplantation (CTA) should continuously be re-addressed to ensure that positive but realistic expectations are maintained, especially in light of the relatively young age of CTA transplantation. Further psychiatric assessment and treatment may be needed based on individual results to prevent an adverse postoperative emotional reaction and to ensure that the stress or anxiety related to the procedure, recovery, and new limb is addressed and kept to a minimum.
After the hand transplant recipient is discharged from the hospital, laboratory values and clinical status need to be monitored weekly for several months, and any suspicious changes should be reported to the appropriate treating physician. The patient should reside near the hospital for 12 weeks after surgery, and the coordinator should be available at any time to respond to the patient’s concerns. After the 12-week postoperative period, the transplant coordinator should arrange follow-up at 3 months, 6 months, 1 year, and annually thereafter.
The coordinator is responsible for helping to plan the hand transplant recipient’s transition to home. Arrangements should be made before surgery for a mirror team to monitor the patient’s care in the patient’s hometown. The mirror team should consist of an internist, physical therapist with knowledge of hand therapy, and a hand surgeon or other surgeon who can obtain biopsy specimens if necessary. Significant transplant-related illnesses are usually treated by the original transplantation team, and any coexisting medical conditions, such as hypertension or diabetes, can be managed by the patient’s primary care physician. The hand transplant coordinator is responsible for coordinating such care.
During follow-up visits, the therapist should administer quantitative tests of upper limb function as needed. The criterion standard test administered after hand transplant is the Carroll test, which assesses the patient's ability to perform activities of daily life that involve the upper limbs. In addition, the DASH (disabilities of the arm, shoulder, and hand) score has been used to evaluate hand transplantation functional ability.
In order to analyze functional results in a standardized way, the International Hand Registry has developed a functional score system. The Hand Transplantation Score System (HTSS) evaluates the following 6 aspects for a total of 100 points: appearance, sensibility, movement, psychological and social acceptance, daily activities and work status, and patient satisfaction and general well-being.
Early postoperative complications
Early postoperative complications include vascular thrombosis, limb loss, bleeding, surgical wound infection, deep venous thrombosis (DVT), increased risk of infection such as pneumonia and cytomegalovirus (CMV) infection, and other complications related to a prolonged surgical procedure and immunosuppressive therapy.Issues with revascularization like thrombosis are very rare and are dependent on the microsurgical skills of the team. In such an event, vascular exploration is performed and anastomoses redone, either end-to-end or end-to-side, as indicated. Edema in the postoperative phase is rare and is managed conservatively by elevation and compressive bandaging, as indicated. If venous stasis or lymphedema is suspected clinically, appropriate investigations (venograms or lymphangiograms) are performed to exclude these conditions. Limb volumetry is performed during the early therapy phase to identify and monitor subtle volumechange.
As with any other solid organ transplantation, acute rejection after transplantation and intermittent episodes of acute rejection are relatively simple to reverse by increasing the dose of immunosuppressive agents temporarily and using steroid boluses or topical immunosuppressive and steroidal creams. Acute rejection in hand transplantation is easier to diagnose than in solid organ transplantation, as changes can be noted in the appearance of skin and in biopsy findings. Typical rejection episodes present with a maculopapular patchy rash with or without swelling of the hand. Because of the ease of diagnosis, acute rejections in composite tissue allotransplantation (CTA) may be diagnosed earlier than those for solid organs. As of the end of 2008, all treated acute rejection episodes had been completely reversed.
Osteonecrosis of the hip
Screen patients early (within a year) for asymptomatic disease with bilateral hip MRI; recheck annually after transplant.
Minimize the use of bolus steroids for treatment of rejection.
Use steroid-free protocols, if possible, to reduce risk of this steroid-associated complication.
Neuromas and regional pain syndrome
Neuroma formation and regional pain syndrome are other complications that may occur with any complicated upper extremity nerve attachment.
Psychological considerations and body image disorders need to be addressed with meticulous psychosocial screening and follow-up.
The risks of hand transplantation are similar to those for other forms of organ transplantation followed by immunosuppression. Potential complications of prolonged immunosuppression include increased risk of bacterial, chronic viral, and fungal infections; as well as increased risk of malignancy, nephrotoxicity, neurotoxicity, gastrointestinal toxicity, hypertension, and diabetes, which are all related to the immunosuppressive medication. As of the end of 2008, most complications were transient or reversible. No graft versus host disease, no chronic rejection, and no malignancies or life-threatening conditions due to hand transplantation were reported. Success rates for graft survival in the American and European hand transplants have been higher than rates for other forms of solid organ transplants (96%).[2, 1, 9]
Despite the success of hand transplantation with proper immunosuppression and follow-up, proper safety measures must be put in place. An exit strategy in case of failure is simple and would involve amputation followed by use of prosthesis or another transplant.
Outcome and Prognosis
Unlike solid organ transplantation, hand transplantation to date has been performed in healthy individuals with normal life expectancy. Whether the incidence of chronic rejection in composite tissue allotransplantation (CTA) will be similar to that in solid organs (which occurs nearly a decade after transplantation), remains to be seen. This could be a potential dilemma in a healthy patient who will likely outlive his or her transplanted limb. In the worst-case scenario, the limb can be amputated with no devastating consequences. As of the end of 2008, the longest transplanted hand was 10 years out and free of any evidence of chronic rejection. Unlike other solid organ transplantations, the transplanted hand contains bone marrow; hence, the hypothesis is that partial tolerance is higher and perhaps responsible for this lack of chronic rejection in hand transplantation.
From a functional standpoint, satisfactory-to-excellent recovery of sensibility and motor function has been documented in transplanted hands. Return of 2-point discrimination in most cases and protective sensation in all cases have been documented. Studies of functional MRIs of the brains of these individuals demonstrate that their corresponding homunculus reorganizes and recognizes the new hand. Most patients have reported improved manual skills with return to work.
Recipients have accepted the new hands as their own. In addition to improvement of body image, reports are encouraging regarding improved overall quality of life.
Future and Controversies
The questionable outcome of above-elbow transplantation has been debated. The outcome of the first bilateral above-elbow transplant performed in Munich, Germany, in 2008, may shed some light on this question.
New strategies with allogeneic stem cell transplantation and other cellular therapeutic strategies to induce tolerance are now being explored extensively.[20, 21] These options, in conjunction with the use of steroid-free and less toxic immunosuppressive medications, can significantly impact the success of hand transplantations in the future and will therefore redefine the future of reconstructive surgery using composite tissue allotransplantation (CTA).
7th International Symposium on Composite Tissue Allotransplantation. Sept 7-8th 2007. Available at http://cta2007.uklibk.ac.at/page.cfm?vpath=index.
www.handregistry.com (The International Registry on Hand and Composite Tissue Transplantation ). Accessed 7/2/09;
Tobin GR, Breidenbach WC, Klapheke MM, et al. Ethical considerations in the early composite tissue allograft experience: a review of the Louisville Ethics Program. Transplant Proc. 2005 Mar. 37(2):1392-5. [Medline].
Chad R. Gordon, Joseph M. Serletti, Kirby S. Black and Charles W. Hewitt. The Evolution of Composite Tissue Allotransplantation: the Twentieth Century Realization of. Charles W. Hewitt, W. P. Andrew Lee and Chad R. Gordon. Transplantation of Composite Tissue Allografts. Springer US; 2007. 13-25.
Jones JW, Gruber SA, Barker JH, et al. Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team. N Engl J Med. 2000 Aug 17. 343(7):468-73. [Medline].
Tobin GR, Breidenbach WC 3rd, Pidwell DJ, et al. Transplantation of the hand, face, and composite structures: evolution and current status. Clin Plast Surg. 2007 Apr. 34(2):271-8, ix-x. [Medline].
Amirlak B. Personal communication, Breidenbach W. During hand transplantation. Louisville, Ky: Jewish Hospital Hand Care Center; Nov 30, 2006.
www.handtransplant.com. Available at www.handtransplant.com. Accessed: June 30/08.
Lanzetta M, Petruzzo P, Dubernard JM, et al. Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation. Transpl Immunol. 2007 Jul. 18(1):1-6. [Medline].
Amirlak B, Gonzalez R, Gorantla V, et al. Creating a hand transplant program. Clin Plast Surg. 2007 Apr. 34(2):279-89, x. [Medline].
Klapheke MM, Marcell C, Taliaferro G, et al. Psychiatric assessment of candidates for hand transplantation. Microsurgery. 2000. 20(8):453-7. [Medline].
Cendales LC, Kirk AD, Moresi JM, et al. Composite tissue allotransplantation: classification of clinical acute skin rejection. Transplantation. 2006 Feb 15. 81(3):418-22. [Medline].
Schneeberger S, Gorantla VS, van Riet RP, et al. Atypical acute rejection after hand transplantation. Am J Transplant. 2008 Mar. 8(3):688-96. [Medline].
Golshayan D, Pascual M. Drug-minimization or tolerance-promoting strategies in human kidney transplantation: is Campath-1H the way to follow?. Transpl Int. 2006 Nov. 19(11):881-4. [Medline].
Scheker LR, Chesher SP, Netscher DT, et al. Functional results of dynamic splinting after transmetacarpal, wrist, and distal forearm replantation. J Hand Surg [Br]. 1995 Oct. 20(5):584-90. [Medline].
Scheker LR, Hodges A. Brace and rehabilitation after replantation and revascularization. Hand Clin. 2001 Aug. 17(3):473-80. [Medline].
carroll D. A quantitive test of upper extremity function. J Chronic Dis. 1965. 18:479-91.
Gonzalez, Ruben N.; Gorantla, Vijay S.; Breidenbach, Warren C. Complications after Hand Transplantation: Preliminary Report of Osteonecrosis in the Second American Patient. Journal of Reconstructive Microsurgery. August 2005. 21(6):425.
Amirlak B, Gorantla V, Gonzalez R, Breidenbach W. Updates on the Three American Hand Transplants. June-2007.
Muramatsu K, Kuriyama R, You-Xin S, et al. Chimerism studies as an approach for the induction of tolerance to extremity allografts. J Plast Reconstr Aesthet Surg. 2008 Sep. 61(9):1009-15. [Medline].
Amirlak B. Personal communication, Starzl TE and Gorantla V. Seefeld, Austria: 7th International Symposium for Composite Tissue Allotransplantation; Sept 9, 2007.
|Date||Single Hand Transplantation||Double Hand Transplantation||Digital Transplantation|
|Sep 1998||Lyon (1)|
|Jan 1999||Louisville (1)|
|Sep 1999||Guangzhou (2)|
|Jan 2000||Nanning (2)||Lyon (1)||Nanning (1)|
|Mar 2000||Innsbruck (1)|
|May 2000||Kuala-Lumpur (1)
Twins - no immunosuppression required
|Sep 2000||Guangzhou (1)|
|Oct 2000||Milan (1)|
|Nov 2000||Nanning (2)|
|Jan 2001||Harbin (1)|
|Feb 2001||Louisville (1)|
|Oct 2001||Milan (1)|
|Jun 2002||Bruxelles (1)|
|Jun 2002||Harbin (1)|
|Jul 2002||Nanjin (1)|
|Oct 2002||Harbin (1)|
|Nov 2002||Milan (1)|
|Feb 2003||Innsbruck (1)|
|Apr 2003||Lyon (1)|
|Feb 2005||Nanjin (1)|
|Jun 2006||Innsbruck (1)|
|Feb 2006||Wroclaw (1)|
|Nov 2006||Louisville (1)|
|Dec 2006||Valencia (1)|
|Feb 2007||Lyon (1)|
|Nov 2007||Valencia (1)|
|Jan 2008||Wroclaw (1)|
|July 2008||Louisville (1)|
|Jul 2008||Munich (1)|
|Nov 2008||Louisville (1)|
|Feb 2009||Pittsburg (1)|
|March 2009||Paris (1)
Simultaneous with face
|July 2009||Lyon (1)|
|Feb 2010||San Antonio (1)|
|2011||Los Angeles (1)|
|2011||Mexico City (1)|