Skip to main content

Advertisement

SpringerLink
Log in

Upper extremity transplantation: current concepts and challenges in an emerging field

  • Hand and Wrist: Plastics (DT Fufa, Section editor)
  • Published:
Current Reviews in Musculoskeletal Medicine Aims and scope Submit manuscript

Abstract

Loss of an isolated upper limb is an emotionally and physically devastating event that results in significant impairment. Patients who lose both upper extremities experience profound disability that affects nearly every aspect of their lives. While prosthetics and surgery can eventually provide the single limb amputee with a suitable assisting hand, limited utility, minimal haptic feedback, weight, and discomfort are persistent problems with these techniques that contribute to high rates of prosthetic rejection. Moreover, despite ongoing advances in prosthetic technology, bilateral amputees continue to experience high levels of dependency, disability, and distress. Hand and upper extremity transplantation holds several advantages over prosthetic rehabilitation. The missing limb is replaced with one of similar skin color and size. Sensibility, voluntary motor control, and proprioception are restored to a greater degree, and afford better dexterity and function than prosthetics. The main shortcomings of transplantation include the hazards of immunosuppression, the complications of rejection and its treatment, and high cost. Hand and upper limb transplantation represents the most commonly performed surgery in the growing field of Vascularized Composite Allotransplantation (VCA). As upper limb transplantation and VCA have become more widespread, several important challenges and controversies have emerged. These include: refining indications for transplantation, optimizing immunosuppression, establishing reliable criteria for monitoring, diagnosing, and treating rejection, and standardizing outcome measures. This article will summarize the historical background of hand transplantation and review the current literature and concepts surrounding it.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Grob M, Papadopulos NA, Zimmerman A, et al. The psychological impact of severe hand injury. J Hand Surg Eur. 2008;33:358–62.

    Article  CAS  Google Scholar 

  2. Grunert BK, Smith CJ, Devine CA, et al. Early psychological aspects of severe hand injury. J Hand Surg (Br). 1998;13:177–80.

    Article  Google Scholar 

  3. Wright TW, Hagen AD, Wood MB. Prosthetic usage in major upper extremity amputations. J Hand Surg [Am]. 1995;20:619–22.

    Google Scholar 

  4. Foroohar A, Elliott RM, Kim TWB, et al. The history and evolution of hand transplantation. Hand Clin. 2011;27:405–9.

    Article  PubMed  Google Scholar 

  5. Peacock EE. A review of composite tissue allografts of the digital flexor mechanism. TPS. 1976;8:119–27.

    Google Scholar 

  6. Peacock EE. Homologous composite tissue grafts of the digital flexor mechanism in human beings. Transplant Bull. 1960;7:418–21.

    Article  PubMed  Google Scholar 

  7. Peacock EE, Madden JW. Human composite flexor tendon allografts. Ann Surg. 1967;166:624–9.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Gilbert R. Transplant is successful with a cadaver forearm. Med Trib Med News. 1964;5:20–3.

    Google Scholar 

  9. Benhaim P, Anthony JP, Lin LY, et al. A long-term study of allogenic rat hindlimb transplants immunosuppressed with RS-61443. Transplantation. 1993;56:911–7.

    Article  CAS  PubMed  Google Scholar 

  10. Ustuner ET, Zdichavsky M, Ren X, et al. Long-term composite tissue allograft survival in a porcine model with cyclosporine/mycophenolate mofetil therapy. Transplantation. 1998;66:1581–7.

    Article  CAS  PubMed  Google Scholar 

  11. Jones Jr JW, Ustuner ET, Zdichavsky, et al. Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy. Surgery. 1999;126:384–8.

    Article  PubMed  Google Scholar 

  12. Dubernard JM, Owen E, Lefranois N, et al. First human hand transplantation case report. Transpl Int. 2000;13:S521–7.

    Google Scholar 

  13. Dubernard JM, Owen E, Herzberg G, et al. Human hand allograft: report on first 6 months. Lancet. 1999;353:1315–20.

    Article  CAS  PubMed  Google Scholar 

  14. Jones JW, Gruber SA, Barker JH, et al. Successful hand transplantation. One year follow-up. Louisville hand transplant team. N Engl J Med. 2000;343:468–73.

    Article  CAS  PubMed  Google Scholar 

  15. Breidenbach WC, Gonzales R, Kaufman CL, et al. Outcomes of the first 2 American hand transplants at 8 and 6 years post-transplant. J Hand Surg. 2008;33:1039–47.

    Article  Google Scholar 

  16. Pertuzzo P, Badet C, Gazarian A, et al. Bilateral hand transplantation: six years after the first case. Am J Transplant. 2006;6:1718–24.

    Article  Google Scholar 

  17. Hollenbeck ST, Erdmann D, Levin LS. Current indications for hand and face transplantation. Transplant Proc. 2009;41:495–8.

    Article  CAS  PubMed  Google Scholar 

  18. Petruzzo P, Lanzetta M, Dubernard JM, et al. The international registry on hand and composite tissue transplantation. Transplantation. 2010;90:1590–4.

    Article  PubMed  Google Scholar 

  19. • Petruzzo P, Dubernard JM. The international registry on hand and composite tissue allotransplantation. Clin Transpl. 2011:247–53. Reports the most current aggregate data from the international hand transplant registry. Note that several leading centers do not share data with the registry.

  20. Brandacher G, Ninkovic M, Piza-Katzer H, et al. The Innsbruck hand transplant program: update at 8 years after the first hand transplant. Transplant Proc. 2009;41:491–4.

    Article  CAS  PubMed  Google Scholar 

  21. Cavadas PC, Ibanez J, Thione A, et al. Bilateral trans-humeral arm transplantation: result at 2 years. Am J Transplant. 2011;11:1085–90.

    Article  CAS  PubMed  Google Scholar 

  22. Stangl MJ, Biemer E, Nerlich A, et al. Three year immunological follow-up of the first bilateral arm transplant world-wide. Transplantation. 2012;94:346.

    Article  Google Scholar 

  23. Jensen SE, Butt Z, Bill A, et al. Quality of life considerations in upper limb transplantation: review and future directions. J Hand Surg [Am]. 2012;37:2126–35.

    Article  Google Scholar 

  24. Murray JE. Organ transplantation (skin, kidney, heart) and the plastic surgeon. Plast Reconstr Surg. 1971;47:425–31.

    Article  CAS  PubMed  Google Scholar 

  25. Brouha P, Naidu D, Cunningham M, et al. Risk acceptance in composite-tissue allotransplantation reconstructive procedures. Microsurgery. 2006;26:144–9.

    Article  PubMed  Google Scholar 

  26. Brandacher G, Gorantla VS, Lee WP. Hand allotransplantation. Semin Plast Surg. 2010;24:11–7.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Schneeberger S, Gorantla VS, Hautz T, et al. Immunosuppression and rejection in human hand transplantation. Transplant Proc. 2009;41:472–5.

    Article  CAS  PubMed  Google Scholar 

  28. Shores JT, Imbriglia JE, Lee WP. The current state of hand transplantation. J Hand Surg [Am]. 2011;36:1862–7.

    Article  Google Scholar 

  29. Hautz T, Brandacher G, Zelger B, et al. Immunologic aspects and rejection in solid organ vs reconstructive transplantation. Transplantation. 2010;42:3347–53.

    CAS  Google Scholar 

  30. •• Schneeberger S, Gorantla VS, Brandacher G, et al. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013;257:345–51. Outlines the “Pittsburgh Protocol”- a novel and promising method that uses donor bone marrow infusion at the time of transplant in an attempt to induce chimerism in the recipient leading to single drug immunosuppression.

    Article  PubMed  Google Scholar 

  31. Starzl TE, Zinkernagel RM. Antigen localization and migration in immunity and tolerance. N Engl J Med. 1998;339:1905–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Starzl TE, Murase N, Abu-Elmagd, et al. Tolerogenic immunosuppression for organ transplantation. Lancet. 2003;361:1502–10.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Fontes P. Bone marrow augmentation of donor-cell chimerism in kidney, liver, heart, and pancreas islet transplantation. Lancet. 1994;344:151–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Ciancio G, Miller J, Garcia-Morales RO, et al. Six-year clinical effect of donor bone marrow infusions in renal transplant patients. Transplantation. 2001;71:827–35.

    Article  CAS  PubMed  Google Scholar 

  35. Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature. 1984;307:168–70.

    Article  CAS  PubMed  Google Scholar 

  36. Wu S, Xu H, Ravindra K, et al. Composite tissue allotransplantation: past, present, and future-the history and expanding applications of CTA as a new frontier in transplantation. Transplant Proc. 2009;41:463–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Birch R. Nerve repair. In: Wolfe SW, Hotchkiss RN, Pederson WC, Kozin SH, editors. Green’s operative hand surgery. Philadelphia: Elsevier; 2011. p. 1035–74.

    Chapter  Google Scholar 

  38. Tanaka K, Fujita N, Higashi Y, et al. Neuroprotective and antioxidant properties of FKBP-binding immunophilin ligands are independent on the FKBP12 pathway in human cells. Neurosci Lett. 2002;330:147–50.

    Article  CAS  PubMed  Google Scholar 

  39. Yan Y, Sun HH, Hunter DA, et al. Efficacy of short-term FK506 administration on accelerating nerve regeneration. Neurorehabil Neural Repair. 2012;26:570–80.

    Article  PubMed  Google Scholar 

  40. Moore AM, Ray WZ, Chenard KE, et al. Nerve allotransplantation as it pertains to composite tissue transplantation. Hand. 2009;4:239–44.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Mackinnon SE, Doolabh VB, Novack CB, et al. Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg. 2001;107:1419–29.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

River M. Elliott declares that he has no conflict of interest. Scott M. Tintle declares that he has no conflict of interest. L. Scott Levin declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

Author information

Authors and Affiliations

  1. The Curtis National Hand Center, 3333 North Calvert Street, Baltimore, MD, 21209, USA

    River M. Elliott

  2. Department of Orthopaedic Surgery, Walter Reed National Military Medical Center, America Building, 19 2nd Floor, Bethesda, MD, 20889-5600, USA

    Scott M. Tintle

  3. Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, 2 Silverstein, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    L. Scott Levin

Authors
  1. River M. Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott M. Tintle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Scott Levin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Scott Levin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elliott, R.M., Tintle, S.M. & Levin, L.S. Upper extremity transplantation: current concepts and challenges in an emerging field. Curr Rev Musculoskelet Med 7, 83–88 (2014). https://doi.org/10.1007/s12178-013-9191-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12178-013-9191-x

Keywords

Search

Navigation