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A Survey of North American Hand Surgeons on Their Current Attitudes Toward Hand Transplantation
SCIENTIFIC ARTICLE
A Survey of North American Hand Surgeons on Their Current Attitudes Toward Hand Transplantation David W. Mathes, MD, Robert Schlenker, MD, Emilia Ploplys, MD, Nicholas Vedder, MD Purpose Although composite tissue allotransplantation (CTA) is unparalleled in its potential to reconstruct “like with like,” the risk– benefit ratio and clinical indications are difficult to determine. We examined current attitudes regarding the emerging field of CTA from those who treat complex hand injuries. Methods A web-based survey regarding CTA was sent to members of the American Society for Surgery of the Hand, which identified their demographic data and practice profiles. Respondents’ support for CTA and their assessment of the level of risk associated with these procedures were addressed. Additional questions focused on the clinical application of CTA with current immunosuppression, ethical issues surrounding CTA, and the indications for hand transplantation. Finally, 2 clinical situations that closely mirrored past hand transplantations were presented, and members evaluated their suitability for allotransplantation. Results A total of 474 surgeons responded to the survey (22% response rate), who were divided in their opinion of hand transplantation with 24% in favor, 45% against, and 31% undecided. The majority (69%) consider this surgery to be a high-risk endeavor; however, a large percentage (71%) still believe it to be an ethical procedure when performed on properly selected patients. The most accepted indications for hand transplantation were loss of bilateral hands (78%) and amputation of a dominant hand (32%). Only 16% were in favor of performing transplants with the immunosuppression available today. In response to the clinical situation, 66% would offer transplantation to a bilateral hand amputee, whereas only 9% would offer transplantation to a patient with diabetes who had lost his or her dominant hand. Conclusions This survey demonstrates support for hand allotransplantation as a solution for dominanthand and bilateral hand amputees. However, surgeons continue to be concerned about the adverse effects of immunosuppression and the risks of acute and chronic rejection, and many want to wait for the development of better immunologic treatment options. (J Hand Surg 2009;34A:808–814. © 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) Key words Composite tissue allotransplantation, Hand transplantation, Complex hand injury, Immunosuppression, Survey.
consist of several tissue components, including skin, subcutaneous tissue, muscle, bone, cartilage, tendon, nerve, and blood vessels. Unlike traditionally transplanted
C
OMPOSITE TISSUE ALLOGRAFTS
From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Washington, Seattle, WA. Received for publication October 11, 2008; accepted in revised form January 20, 2009. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
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solid organs (kidney, liver, and heart), which consist of relatively homogeneous parenchymal tissue, composite tissue allografts are histologically heterogeneous and composed of tissues with different degrees Corresponding author: David W. Mathes, MD, University of Washington Medical Center, Department of Surgery, 1959 Pacific Ave., Box 356410, Seattle, WA 98195; e-mail: [email protected]. 0363-5023/09/34A05-0002$36.00/0 doi:10.1016/j.jhsa.2009.01.021
SURVEY ON ATTITUDES TOWARD HAND TRANSPLANTATION
of antigenicity that can elicit a strong immune response.1,2 Composite tissue allotransplantation (CTA) is an emerging area in reconstructive surgery. It has the potential to combine the principles of microvascular reconstructive surgery with those of organ transplantation. The initial clinical feasibility of CTA has been substantiated by the successful transplantation of 41 hands, 16 larynges, 3 partial faces, and 9 abdominal walls (data from www.handregistry. com).3–12 Although solid organ transplantation is widely accepted in the medical community as the best treatment of end-stage organ failure, there remain strong differences in opinion concerning the utility of CTA for hand transplantation.13–19 The proponents of hand transplantation see it as an opportunity to truly restore function to those who have lost their hands. It could be the ultimate option in functional reconstruction, with unparalleled potential to restore “like with like” while avoiding donor-site morbidity. They argue that initial experimental trial outcomes have been encouraging, with functional recovery comparable to upper extremity replantation. In addition, these transplants have led to an enhancement of activities of daily living, restoration of activities not afforded by a prosthesis, patient satisfaction, low to moderate morbidity, and no mortality. The critics of CTA express concern over a lack of convincing scientific data, unclear risk– benefit ratio, and uncertain long-term functional results. These surgeons feel that it is unwarranted to subject disabled but healthy patients to the adverse effects of chronic immunosuppression (such as opportunistic infections, increased risk of malignancy, or possible organ dysfunction). These hand transplants are not lifesaving procedures but only serve to improve the recipients’ quality of life. In addition, it is felt that unilateral and bilateral upper limb amputees already have a variety of prostheses to choose from that can improve their quality of life without being potentially life threatening. In this study, we sought to examine the current attitudes regarding the emerging field of CTA, in particular hand transplantation, from those who treat complex hand injuries. We also wished to see whether these attitudes have changed with increased length of follow-up for those that have had hand transplantation. MATERIALS AND METHODS In 2007, a survey was devised to determine current attitudes toward the evolving field of CTA from hand surgeons in the United States. This web-based survey was sent to all active members of the American Society for Surgery of the Hand (ASSH) via e-mail. The survey
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consisted of 18 questions (see Appendix, which can be viewed at the Journal’s Web site, http://www.jhandsurg. org) and was blinded to enhance the response rate, ensure that each response remained anonymous, and minimize bias. The initial portion of the survey sought to define the demographic data and practice profiles of the respondents. These questions related to the extent of their training in hand surgery (areas of certification and accreditation) and years in practice. Additional questions examined the respondents’ practice experience with complex hand injuries through their personal assessment of the number of digital replants, hand replants, and functional free tissue transfers (toe to thumb) performed annually. The next section examined the respondents’ attitudes about the field of CTA. In order to compare responses, these questions consisted of the closed-response checkbox design. Respondents were asked to provide information regarding their current position on CTA (in favor, against, or undecided). They were also asked whether this opinion had changed after the reports of successful clinical hand transplants. The subsequent questions concentrated on their assessment of the level of risk associated with hand transplantation, face transplantation, abdominal wall transplantation, and free tissue transfer surgeries (such as toe-to-thumb reconstruction). We then sought to explore the surgeons’ support for the clinical application of CTA with current immunosuppression versus the need for either more long-term follow-up, new immunosuppressive agents, or the induction of tolerance. We also examined the ethical issues surrounding CTA and asked them to evaluate the indications for CTA in complex hand injures. In an effort to get an idea about the number of potential hand transplant recipients in the community, respondents were asked how many patients they had seen in their career that met their indications for hand transplantation. Finally, 2 clinical situations that mirrored actual clinical patients that have had hand transplantation were presented, and members were asked to evaluate each patient’s suitability for CTA (Appendix, questions 17 and 18; the Appendix can be viewed at the Journal’s Web site, http://www.jhandsurg.org). Data were collected and response percentages were calculated. RESULTS Demographics and practice profile Of the 2,150 ASSH members contacted, 474 responded to the survey (22% response rate). The respondents
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FIGURE 1: This figure shows the percentage of surveyed ASSH members with residency training in orthopedic surgery, plastic surgery, and general surgery. This figure also shows the percentage of members who subsequently completed a hand fellowship.
averaged 15 years in practice, and most had residency training in orthopedic (N ⫽ 298, 63%) or plastic surgery (N ⫽ 104, 22%), with the remainder having trained in general surgery (N ⫽ 40). Three hundred forty (72%) subsequently completed a hand fellowship (Fig. 1). They performed on average of approximately 10 upper extremity replantations per year and 1 functional free tissue (such as toe-to-thumb) transfer per year. They also reported having done an average of 7 total hand replantations during their surgical careers. The high number of functional free tissue transfers is due to 9 respondents who reported performing 10 or more toe-to-thumb surgeries per year. If these few outlying responses are eliminated, the overall rate for hand surgeons performing this procedure is less than 1 per year. Level of risk in composite tissue allotransplantation The majority (N ⫽ 327, 69%) of respondents assessed hand transplantation as a high-risk endeavor (Table 1). In contrast, respondents thought that toe-to-thumb reconstruction was a medium- (N ⫽ 235, 50%) to lowrisk procedure (N ⫽ 201, 42%). Although outside their field of interest, as indicated by a higher level of responses that they could not make a determination of risk, those who responded also perceived facial transplantation (N ⫽ 261, 55%) and abdominal wall transplantation (N ⫽ 189, 40%) as high-risk procedures. Support and indications for composite tissue allotransplantation The 474 surveyed members were divided in their opinion of hand transplantation, with 113 respondents
TABLE 1. Level of Risk Associated With Hand Transplantation What Level of Risk Do You Assess to a Hand Allotransplant?
Frequency
Percentage (%)
High risk
327
69%
Medium risk
114
24%
8
2%
24
5%
Low risk Cannot assess risk level
(24%) in favor of hand transplantation, 214 (45%) against hand transplantation, and 147 (31%) undecided. When asked if the relative success of the hand transplants performed worldwide had changed their opinions, 4% (N ⫽ 20) of those now in favor had changed their views after the performance of these clinical cases. Only 4 respondents (⬍1%) have actually changed their opinion from favorable to unfavorable after the clinical hand transplants. In terms of the clinical application of hand transplantation, 74 (16%) are in favor of performing transplants with the current available immunosuppression regimen. Another 63 (13%) of those responding would be willing to use the current immunosuppression regimen only after there have been satisfactory results with at least a 10-year follow-up. The majority of surgeons wished to wait for the development of new techniques that would lead to immunologic tolerance (N ⫽ 180, 38%) or an advanced immunosuppressive regimen (N ⫽ 108, 23%) before endorsing hand transplantation (Table 2). Only 49 surgeons (10%) felt that there were no indications
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TABLE 2. Clinical Application of Hand Transplantation Clinical Application of Hand Allotransplantation
TABLE 4. Ethics in Hand Transplantation
Frequency
Percentage (%)
Is acceptable with the current immunosuppression offered today
74
15%
Would only be acceptable if current transplants are shown to be viable at 10 years
63
13%
Would only be acceptable with a more advanced immunosuppressive regimen
108
23%
Would only be acceptable if immunologic tolerance to the graft could be achieved
180
38%
49
10%
Is not justifiable
TABLE 3.
Indications for Hand Transplantation
Indications for Hand, Partial Hand, or Digit Allotransplantation Should Include
Frequency
Percentage (%)
Amputation of bilateral hands
366
78%
Amputation of dominant hand
148
32%
Multiple failed reconstructions (e.g., failed toe to thumb)
127
27%
92
20%
Amputation of thumb Amputation of multiple digits
79
17%
Amputation of non-dominant hand
65
14%
There is no acceptable indication for hand transplantation
81
17%
for hand transplantation in any situation. When respondents were asked about the number of patients they had seen in their career who met their indications for hand transplantation, the average was approximately 1.35 patients per surgeon. The most accepted indications for hand transplantation were loss of bilateral hands (N ⫽ 366, 78%) followed by amputation of a dominant hand (N ⫽ 149, 32%) (Table 3). However, there was also support (N ⫽ 128, 27%) for hand transplantation in those patients who had failed multiple reconstructions (such as loss of toe-to-thumb). The majority of the surgeons did not feel that transplantation of the nondominant hand was an indication for hand transplantation, as evidenced by a low level of support (N ⫽ 66, 14% in favor of these transplants).
Hand Transplantation Is an Ethical Procedure if Performed on a Properly Selected Patient Strongly agree
Frequency
Percentage (%)
62
13%
Agree
272
58%
Disagree
105
22%
34
7%
Strongly disagree
Ethics in composite tissue allotransplantation Seventy-one percent (N ⫽ 335) believe that hand transplantation is an ethical procedure when performed on a properly selected patient (Table 4). Clinical cases for composite tissue allotransplantation In response to clinical situations mimicking past hand transplantations, 313 (66%) would offer transplantation to a bilateral hand amputee, whereas only 41 (9%) would offer transplantation to a patient with diabetes who had lost his or her dominant hand. DISCUSSION The traumatic amputation of a patient’s hand is a disfiguring event with immeasurable personal, psychological, financial, and social implications in addition to the obvious functional limitations. The ability to safely transplant a fully integrated and functional hand to these amputees would be of tremendous reconstructive value. Currently, clinical hand transplantation remains an experimental procedure, and the outcomes of this innovative procedure are still being determined. In the current era of immunosuppression, 41 hand transplantations have been performed on 30 patients. The results thus far have been promising, with most patients reporting varying degrees of return of function.3–5 The longest follow-up available is from the second hand transplant performed by the group in Louisville; the patient is now almost 9 years postoperative with a functioning hand.20 –22 In a recent article, the group in Louisville reported detailed outcomes of the first 2 American hand transplant recipients at 8 and 6 years post-transplantation. Both patients have allograft survival, with improvements in intrinsic muscle activity, total active motion, and return of functional grip, pinch strength, and sensibility. The latest Carroll test scores, which measure the patients’ ability to perform tasks requiring a combination of mobility, motor function, and sensation, are fair for patient 1 (72/99) and fair for patient 2 (55/99).
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These Carroll test scores exceed the expected results of 20 –30 of 99 that would be achieved with a prosthetic hand. The first patients’ Semmes-Weinstein monofilament sensation testing is in the normal range for all fingertips, and the patient has shown improvement in both static 2-point discrimination and moving 2-point discrimination over previous testing. Touch localization, stereognosis, and temperature and vibration sensation have also returned. The second patient has not demonstrated a similar return of sensation through year 6; however, in 2008, his protective sensation was noted to have returned.22 In 2003, the ASSH reviewed its position paper regarding hand transplantation. They concluded, based on the clinical experience of 14 patients, that hand transplantation should still be considered an experimental procedure that might enhance function or appearance in carefully selected patients. They proposed that additional research and progress in transplant immunology would be needed before hand transplantation could be considered a consistently safe and efficacious practice (www.hand-surg.org; ASSH Public Information. Hand Transplantation: Current Status). In this study, we sought to examine the current attitudes regarding the emerging field of hand transplantation from those who treat complex hand injuries. We also sought to assess the changes in attitudes that might have occurred due to the growing number of hand transplant cases and the increased length of follow-up. Although most hand surgeons can agree that tremendous potential benefits could be achieved from a successful hand transplantation, the surveyed membership remains hesitant to approve the practice. This skepticism is demonstrated by the fact that only 24% of the hand surgeons surveyed were in favor of hand transplantation. The majority of respondents were against hand transplantation (45%) or remained undecided (31%). Twenty respondents (4%) report changing their opinion about hand transplantation and now support transplantation. This may be due in part to their recognition of the relative success of recent hand transplantations. This suggests that hand transplantation could potentially attain more widespread acceptance over time, as additional outcome data regarding long-term functional results become available. Of the 474 members who responded to the survey, 353 (75%) replied that they currently perform microsurgical reconstruction of the hand in the form of digital replantation, hand replantation, or functional free tissue transfers (toe to thumb). A sub-analysis was performed to exclude the 121 members who no longer performed microsurgery
to see whether surgeons who treated complex hand injuries were more inclined to be in favor of hand transplantation. However, when the results were adjusted, the support for hand transplantation remained comparable, with 86 (24%) in favor of hand transplantation, 162 (46%) against hand transplantation, and 105 (30%) undecided. The predominant limiting factor to the clinical application of hand transplantation is the need for chronic immunosuppression. Long-term immunosuppression is associated with many potential adverse effects, including opportunistic infections, malignancies, and organ failure. In addition, all of the hand transplants have experienced episodes of acute rejection that required treatment.3,4,23–26 This might be a result of the relative increase in antigenicity over the more homogenous classic organ allografts due in part to the presence of multiple tissue types (especially the skin). These factors explain the limited support for transplanting hands (only 16% of respondents) with the currently available immunosuppressive regimens. The additional unknown datum is how long these transplants will last. The support for the current regimens would increase by 13% if current transplants were shown to be viable and functional after 10 years. A considerable group of surgeons (28%) stated that they would accept hand transplantation only if a more advanced and less toxic immunosuppressive regimen was developed. The largest group of surgeons (38%) wished to wait for the establishment of immunologic tolerance before proceeding with further transplants. Only 10% of surgeons stated that there was no indication for hand transplantation. A critical issue in terms of the application of hand transplantation in the reconstruction of complex hand injuries is what the accepted indications should be. An overwhelming majority of surgeons (71%) believe that hand transplantation is an ethical procedure when performed on a properly selected patient. This was especially true when they were asked about using hand transplantation to treat bilateral upper extremity amputees (78% in favor of transplantation). The support for other listed indications was not as strong, with only 32% in support of transplantation after amputation of a dominant hand and 27% in cases of multiple failed attempts at reconstruction. There was less support of transplantation to treat an amputated thumb (20%), multiple digits (17%), or a nondominant hand (14%). A small percentage (17%) again responded that there was no indication for hand transplantation. The continued uncertainty about hand transplantation might stem from the attitude shared by 69% of the
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hand surgeons regarding hand transplantation as a highrisk endeavor. These concerns are not unique to hand transplantation but are shared by other types of CTA, as the majority of respondents also perceived facial transplantation and abdominal wall transplantation as highrisk procedures. These concerns were reflected in the proposed clinical situations mimicking past hand transplantation cases, for which 66% offered transplantation to a bilateral hand amputee and only 9% to a patient with diabetes who had lost his or her dominant hand. Surveys are a useful tool for examining current attitudes and practice patterns of physicians. The 22% response rate achieved in our study likely reflects that a large percentage of those who were sent the survey do not perform complex hand microvascular reconstruction and thus did not respond. We sent out the most surveys (N ⫽ 2150) of any recently published ASSH survey and received 474 responses. Previous studies have had higher percentages of responses (28.7% to 45%), but the actual numbers of respondents varied from 280 to 591 surgeons.27–31 The fact that 474 hand surgeons responded to the study indicates that a considerable percentage of ASSH members found the issues addressed in the survey to be important. A limitation of the present study was the possibility of non-respondent bias. Hand surgeons not using their microsurgical training and not treating these types of complex hand injuries and amputations in their current practice may have been less inclined to respond to the survey. It is possible that the responses of these surgeons could have increased the number of those surgeons against hand transplantation. Such bias has been shown to be extremely difficult to prove.32 The results of this survey demonstrate support within the ASSH for continued clinical hand transplantation. This support was strongest for cases of bilateral hand amputation, in which patients have fewer available treatment options. The majority of hand surgeons continue to be wary of the effects of current immunosuppressive regimens and the risks of acute and chronic rejection. The wider application of hand transplantation appears to depend on the development of less toxic immunosuppressive protocols or a future method of tolerance induction. REFERENCES 1. Lee WPA, Yaremchuk MJ, Pan Y-C, Randolph MA, Tan CM, Weiland AJ. Relative antigenicity of components of a vascularized limb allograft. Plast Reconstr Surg 1991;87:401– 411. 2. LLULL R. An open proposal for clinical composite tissue allotransplantation. Transpl Proc 1998;30:2692–2696.
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3. Lanzetta M, Petruzzo P, Margreiter R, Dubernard JM, Schuind F, Breidenbach W, et al. The international registry on hand and composite tissue transplantation. Transplantation. 2005 May;79:1210 – 1214. 4. Lanzetta M, Petruzzo P, Dubernard JM, Margreiter R, Schuind F, Breidenbach W, et al. Second report (1998 –2006) of the international registry of hand and composite tissue transplantation. Transpl Immunol 2007;18:1– 6. 5. Ravindra KV, Wu S, Bozulic L, Xu H, Breidenbach WC, Ildstad ST. Composite tissue transplantation: a rapidly advancing field. Transplant Proc. 2008;40:1237–1248. 6. Birchall M. Human laryngeal allograft: shift of emphasis in transplantation. Lancet 1998;351:539 –540. 7. Strome M, Stein J, Esclamado R, Hicks D, Lorenz RR, Braun W, et al. Laryngeal transplantation and 40-month follow-up. N Engl J Med 2001;344:1676 –1679. 8. Birchall MA, Lorenz RR, Berke GS, Genden EM, Haughey BH, Siemionow M, et al. Laryngeal transplantation in 2005: a review. Am J Transplant 2006;6:20 –26. 9. Devauchelle B, Badet L, Lengelé B, Morelon E, Testelin S, Michallet M, et al. First human face allograft: early report. Lancet 2006; 368:203–209. 10. Dubernard JM, Lengelé B, Morelon E, Testelin S, Badet L, Moure C, et al. Outcomes 18 months after the first human partial face transplantation. N Engl J Med 2007;357:2451–2460. 11. Levi DM, Tzakis AG, Kato T, Madariaga J, Mittal NK, Nery J, et al. Transplantation of the abdominal wall. Lancet 2003;361:2173–2176. 12. Selvaggi G, Levi DM, Kato T, Madariaga J, Moon J, Nishida S, et al. Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation. Transplant Proc 2004;36:1561–1563. 13. Siegler M. Ethical issues in innovative surgery: should we attempt a cadaveric hand transplantation in a human subject? Transplant Proc 1998;30:2779 –2782. 14. Lee WP, Mathes DW. Hand transplantation: pertinent data and future outlook. J Hand Surg 1999;24A:906 –913. 15. Hatrick NC, Tonkin MA. Hand transplantation: a current perspective. ANZ J Surg 2001;71:245–251. 16. Cooney WP, Hentz VR. Hand transplantation—primum non nocere. J Hand Surg 2002;27A:165–168. 17. Breidenbach WC III, Tobin GR II, Gorantla VS, Gonzalez RN, Granger DK. A position statement in support of hand transplantation. J Hand Surg 2002;27A:760 –770. 18. Jones NF. Concerns about human hand transplantation in the 21st century. J Hand Surg 2002;27A:771–787. 19. Lees VC, McCabe SJ. The rationale for hand transplantation. Transplantation 2002;74:749 –753. 20. Jones JW, Gruber SA, Barker JH, Breidenbach WC. Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team. N Engl J Med 2000;343:468 – 473. 21. Tobin GR, Granger DK, Breidenbach WC. Hand transplantation follow-up. Lancet 2001;358:1018. 22. Breidenbach WC, Gonzales NR, Kaufman CL, Klapheke M, Tobin GR, Gorantla VS. Outcomes of the first 2 American hand transplants at 8 and 6 years posttransplant. J Hand Surg 2008;33A:1039 –1047. 23. Dubernard JM, Owen E, Herzberg G, Lanzetta M, Martin X, Kapila H, et al. Human hand allograft: report on first 6 months. Lancet 1999;3531:1315–1320. 24. Kanitakis J, Jullien D, Petruzzo P, Hakim N, Claudy A, Revillard JP, et al. Clinicopathologic features of graft rejection of the first human hand allograft. Transplantation 2003;76:688 – 693. 25. Lineaweaver WC. Chronic rejection, hand transplantation, and the monkey’s paw. Microsurgery 2006;26:419 – 420. 26. Horner BM, Randolph MA, Huang CA, Butler PE. Skin tolerance: in search of the Holy Grail. Transpl Int 2008;21:101–112. 27. McCarthy DM, Boardman ND III, Tramaglini DM, Sotereanos DG, Herndon JH. Clinical management of partially lacerated digital
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flexor tendons: a survey of hand surgeons. J Hand Surg 1995; 20A:273–275. 28. Alderman AK, Chung KC, Kim HM, Fox DA, Ubel PA. Effectiveness of rheumatoid hand surgery: contrasting perceptions of hand surgeons and rheumatologists. J Hand Surg 2003;28A:3–11. 29. Zarkadas PC, Gropper PT, White NJ, Perey BH. A survey of the surgical management of acute and chronic scapholunate instability. J Hand Surg 2004;29A:848 – 857.
30. Mallette P, Ring D. Attitudes of hand surgeons, hand surgery patients, and the general public regarding psychologic influences on illness. J Hand Surg 2006;31A:1362–1366. 31. Payatakes AH, Zagoreos NP, Fedorcik GG, Ruch DS, Levin LS. Current practice of microsurgery by members of the American Society for Surgery of the Hand. J Hand Surg 2007;32A:541–547. 32. Lau FH, Chung KC. Survey research: a primer for hand surgery. J Hand Surg 2005;30A:893–902.
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● ● ● ● ● ●
APPENDIX—SURVEY SENT TO ACTIVE MEMBERS OF THE ASSH Demographics 1) Please check the area(s) in which you are certi-
fied. 2) Please check the area(s) in which you are accred-
ited. 3) How many years have you been in practice? Practice profile 4) Approximately how many digital replantations
15)
do you perform per year? 5) Approximately how many hand replantations have
you performed in your career? 6) Approximately how many functional free tissue
16)
transfers (toe to thumb) for hand reconstruction do you perform per year? Composite tissue allotransplantation 7) Has your opinion regarding the use of composite
8) 9) 10) 11) 12)
13) 14)
tissue allotransplantation to reconstruct complex tissue loss (such as hand amputation) changed? ● Yes, Changed. I am now in favor of hand transplantation ● Yes, Changed. I am now against hand transplantation ● No, Not changed. I am still in favor of hand transplantation ● No, Not changed. I am still against hand transplantation ● Undecided What level of risk do you assess to a hand allotransplant? What level of risk do you assess to a free flap to the hand (toe to thumb transfer)? What level of risk do you assess to facial allotransplantation? What level of risk do you assess to an abdominal wall allotransplant? Clinical application of hand allotransplantationx ● Is acceptable with the current immunosuppression offered today ● Would only be acceptable if current transplants are shown to be viable at 10 years ● Would only be acceptable with a more advanced immunosuppressive regimen ● Would only be acceptable if immunologic tolerance to the graft could be achieved ● Is not justifiable Hand transplantation is an ethical procedure if performed on a properly selected patient. Indications for hand, partial hand, or digit allotransplantation should include:
17)
18)
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Amputation of thumb Amputation of multiple digits Amputation of non-dominant hand Amputation of dominant hand Amputation of bilateral hands Multiple failed reconstructions (e.g., failed toe to thumb) ● There is no acceptable indication for hand transplantation Based on your answers to the above questions, how many patients have you seen in your career that meet your indications for hand transplantation? How many of these patients would meet psychosocial requirements (ability to take immunosuppression, realistic goals, support system, ability to deal with complications, etc.) to undergo hand transplantation? Suppose you are the leader of a well-funded, multidisciplinary hand transplant team with IRB approval to conduct a hand transplantation. Please consider the following case presentations and advise on treatment options. Case 1—You are asked to see a 37-year-old man who lost his dominant left hand and lower forearm 13 years ago in a fireworks accident. He has a myoelectric prosthesis that allows him to work as a paramedic. Past medical history is remarkable for well-controlled type 1 diabetes mellitus for 11 years. The patient is a nonsmoker. He has no evidence of complications of diabetes. He is not satisfied with the functionality of his myoelectric prosthesis after extensive physical therapy and rehabilitation. He has heard about hand transplantation and wants to know if he would be a candidate. You inform him of the current knowledge of risks, benefits, and limitations of hand transplantation as an experimental procedure. You discuss other options for treatment, such as alternate prostheses. He has excellent comprehension of the discussion and desires hand transplantation. You recommend: ● Place the patient on the hand transplantation list. ● Encourage the patient to try a different prosthesis. ● Discourage the patient from further treatment. Case 2—You are asked to see a 31-year-old man who underwent bilateral hand amputation at the distal forearm 6 years ago after a fireworks accident. Although he has completed extensive rehabilitation with his prostheses, he cannot
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complete many activities of daily living. He is otherwise healthy and does not smoke. He has heard about bilateral hand transplantation and wants to know more. You inform him of the current knowledge of risks, benefits, and limitations of hand transplantation as an experimental procedure. You discuss other options for treatment, such as alternate prostheses. He
has excellent comprehension of the discussion and desires bilateral hand transplantation. You recommend: ● Place the patient on the hand transplantation list. ● Encourage the patient to try a different prosthesis. ● Discourage the patient from further treatment.
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A Survey of North American Hand Surgeons on Their Current Attitudes Toward Hand Transplantation David W. Mathes, MD, Robert Schlenker, MD, Emilia Ploplys, MD, Nicholas Vedder, MD Purpose Although composite tissue allotransplantation (CTA) is unparalleled in its potential to reconstruct “like with like,” the risk– benefit ratio and clinical indications are difficult to determine. We examined current attitudes regarding the emerging field of CTA from those who treat complex hand injuries. Methods A web-based survey regarding CTA was sent to members of the American Society for Surgery of the Hand, which identified their demographic data and practice profiles. Respondents’ support for CTA and their assessment of the level of risk associated with these procedures were addressed. Additional questions focused on the clinical application of CTA with current immunosuppression, ethical issues surrounding CTA, and the indications for hand transplantation. Finally, 2 clinical situations that closely mirrored past hand transplantations were presented, and members evaluated their suitability for allotransplantation. Results A total of 474 surgeons responded to the survey (22% response rate), who were divided in their opinion of hand transplantation with 24% in favor, 45% against, and 31% undecided. The majority (69%) consider this surgery to be a high-risk endeavor; however, a large percentage (71%) still believe it to be an ethical procedure when performed on properly selected patients. The most accepted indications for hand transplantation were loss of bilateral hands (78%) and amputation of a dominant hand (32%). Only 16% were in favor of performing transplants with the immunosuppression available today. In response to the clinical situation, 66% would offer transplantation to a bilateral hand amputee, whereas only 9% would offer transplantation to a patient with diabetes who had lost his or her dominant hand. Conclusions This survey demonstrates support for hand allotransplantation as a solution for dominanthand and bilateral hand amputees. However, surgeons continue to be concerned about the adverse effects of immunosuppression and the risks of acute and chronic rejection, and many want to wait for the development of better immunologic treatment options. (J Hand Surg 2009;34A:808–814. © 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) Key words Composite tissue allotransplantation, Hand transplantation, Complex hand injury, Immunosuppression, Survey.
consist of several tissue components, including skin, subcutaneous tissue, muscle, bone, cartilage, tendon, nerve, and blood vessels. Unlike traditionally transplanted
C
OMPOSITE TISSUE ALLOGRAFTS
From the Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Washington, Seattle, WA. Received for publication October 11, 2008; accepted in revised form January 20, 2009. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
808 䉬 © Published by Elsevier, Inc. on behalf of the ASSH.
solid organs (kidney, liver, and heart), which consist of relatively homogeneous parenchymal tissue, composite tissue allografts are histologically heterogeneous and composed of tissues with different degrees Corresponding author: David W. Mathes, MD, University of Washington Medical Center, Department of Surgery, 1959 Pacific Ave., Box 356410, Seattle, WA 98195; e-mail: [email protected]. 0363-5023/09/34A05-0002$36.00/0 doi:10.1016/j.jhsa.2009.01.021
SURVEY ON ATTITUDES TOWARD HAND TRANSPLANTATION
of antigenicity that can elicit a strong immune response.1,2 Composite tissue allotransplantation (CTA) is an emerging area in reconstructive surgery. It has the potential to combine the principles of microvascular reconstructive surgery with those of organ transplantation. The initial clinical feasibility of CTA has been substantiated by the successful transplantation of 41 hands, 16 larynges, 3 partial faces, and 9 abdominal walls (data from www.handregistry. com).3–12 Although solid organ transplantation is widely accepted in the medical community as the best treatment of end-stage organ failure, there remain strong differences in opinion concerning the utility of CTA for hand transplantation.13–19 The proponents of hand transplantation see it as an opportunity to truly restore function to those who have lost their hands. It could be the ultimate option in functional reconstruction, with unparalleled potential to restore “like with like” while avoiding donor-site morbidity. They argue that initial experimental trial outcomes have been encouraging, with functional recovery comparable to upper extremity replantation. In addition, these transplants have led to an enhancement of activities of daily living, restoration of activities not afforded by a prosthesis, patient satisfaction, low to moderate morbidity, and no mortality. The critics of CTA express concern over a lack of convincing scientific data, unclear risk– benefit ratio, and uncertain long-term functional results. These surgeons feel that it is unwarranted to subject disabled but healthy patients to the adverse effects of chronic immunosuppression (such as opportunistic infections, increased risk of malignancy, or possible organ dysfunction). These hand transplants are not lifesaving procedures but only serve to improve the recipients’ quality of life. In addition, it is felt that unilateral and bilateral upper limb amputees already have a variety of prostheses to choose from that can improve their quality of life without being potentially life threatening. In this study, we sought to examine the current attitudes regarding the emerging field of CTA, in particular hand transplantation, from those who treat complex hand injuries. We also wished to see whether these attitudes have changed with increased length of follow-up for those that have had hand transplantation. MATERIALS AND METHODS In 2007, a survey was devised to determine current attitudes toward the evolving field of CTA from hand surgeons in the United States. This web-based survey was sent to all active members of the American Society for Surgery of the Hand (ASSH) via e-mail. The survey
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consisted of 18 questions (see Appendix, which can be viewed at the Journal’s Web site, http://www.jhandsurg. org) and was blinded to enhance the response rate, ensure that each response remained anonymous, and minimize bias. The initial portion of the survey sought to define the demographic data and practice profiles of the respondents. These questions related to the extent of their training in hand surgery (areas of certification and accreditation) and years in practice. Additional questions examined the respondents’ practice experience with complex hand injuries through their personal assessment of the number of digital replants, hand replants, and functional free tissue transfers (toe to thumb) performed annually. The next section examined the respondents’ attitudes about the field of CTA. In order to compare responses, these questions consisted of the closed-response checkbox design. Respondents were asked to provide information regarding their current position on CTA (in favor, against, or undecided). They were also asked whether this opinion had changed after the reports of successful clinical hand transplants. The subsequent questions concentrated on their assessment of the level of risk associated with hand transplantation, face transplantation, abdominal wall transplantation, and free tissue transfer surgeries (such as toe-to-thumb reconstruction). We then sought to explore the surgeons’ support for the clinical application of CTA with current immunosuppression versus the need for either more long-term follow-up, new immunosuppressive agents, or the induction of tolerance. We also examined the ethical issues surrounding CTA and asked them to evaluate the indications for CTA in complex hand injures. In an effort to get an idea about the number of potential hand transplant recipients in the community, respondents were asked how many patients they had seen in their career that met their indications for hand transplantation. Finally, 2 clinical situations that mirrored actual clinical patients that have had hand transplantation were presented, and members were asked to evaluate each patient’s suitability for CTA (Appendix, questions 17 and 18; the Appendix can be viewed at the Journal’s Web site, http://www.jhandsurg.org). Data were collected and response percentages were calculated. RESULTS Demographics and practice profile Of the 2,150 ASSH members contacted, 474 responded to the survey (22% response rate). The respondents
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FIGURE 1: This figure shows the percentage of surveyed ASSH members with residency training in orthopedic surgery, plastic surgery, and general surgery. This figure also shows the percentage of members who subsequently completed a hand fellowship.
averaged 15 years in practice, and most had residency training in orthopedic (N ⫽ 298, 63%) or plastic surgery (N ⫽ 104, 22%), with the remainder having trained in general surgery (N ⫽ 40). Three hundred forty (72%) subsequently completed a hand fellowship (Fig. 1). They performed on average of approximately 10 upper extremity replantations per year and 1 functional free tissue (such as toe-to-thumb) transfer per year. They also reported having done an average of 7 total hand replantations during their surgical careers. The high number of functional free tissue transfers is due to 9 respondents who reported performing 10 or more toe-to-thumb surgeries per year. If these few outlying responses are eliminated, the overall rate for hand surgeons performing this procedure is less than 1 per year. Level of risk in composite tissue allotransplantation The majority (N ⫽ 327, 69%) of respondents assessed hand transplantation as a high-risk endeavor (Table 1). In contrast, respondents thought that toe-to-thumb reconstruction was a medium- (N ⫽ 235, 50%) to lowrisk procedure (N ⫽ 201, 42%). Although outside their field of interest, as indicated by a higher level of responses that they could not make a determination of risk, those who responded also perceived facial transplantation (N ⫽ 261, 55%) and abdominal wall transplantation (N ⫽ 189, 40%) as high-risk procedures. Support and indications for composite tissue allotransplantation The 474 surveyed members were divided in their opinion of hand transplantation, with 113 respondents
TABLE 1. Level of Risk Associated With Hand Transplantation What Level of Risk Do You Assess to a Hand Allotransplant?
Frequency
Percentage (%)
High risk
327
69%
Medium risk
114
24%
8
2%
24
5%
Low risk Cannot assess risk level
(24%) in favor of hand transplantation, 214 (45%) against hand transplantation, and 147 (31%) undecided. When asked if the relative success of the hand transplants performed worldwide had changed their opinions, 4% (N ⫽ 20) of those now in favor had changed their views after the performance of these clinical cases. Only 4 respondents (⬍1%) have actually changed their opinion from favorable to unfavorable after the clinical hand transplants. In terms of the clinical application of hand transplantation, 74 (16%) are in favor of performing transplants with the current available immunosuppression regimen. Another 63 (13%) of those responding would be willing to use the current immunosuppression regimen only after there have been satisfactory results with at least a 10-year follow-up. The majority of surgeons wished to wait for the development of new techniques that would lead to immunologic tolerance (N ⫽ 180, 38%) or an advanced immunosuppressive regimen (N ⫽ 108, 23%) before endorsing hand transplantation (Table 2). Only 49 surgeons (10%) felt that there were no indications
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TABLE 2. Clinical Application of Hand Transplantation Clinical Application of Hand Allotransplantation
TABLE 4. Ethics in Hand Transplantation
Frequency
Percentage (%)
Is acceptable with the current immunosuppression offered today
74
15%
Would only be acceptable if current transplants are shown to be viable at 10 years
63
13%
Would only be acceptable with a more advanced immunosuppressive regimen
108
23%
Would only be acceptable if immunologic tolerance to the graft could be achieved
180
38%
49
10%
Is not justifiable
TABLE 3.
Indications for Hand Transplantation
Indications for Hand, Partial Hand, or Digit Allotransplantation Should Include
Frequency
Percentage (%)
Amputation of bilateral hands
366
78%
Amputation of dominant hand
148
32%
Multiple failed reconstructions (e.g., failed toe to thumb)
127
27%
92
20%
Amputation of thumb Amputation of multiple digits
79
17%
Amputation of non-dominant hand
65
14%
There is no acceptable indication for hand transplantation
81
17%
for hand transplantation in any situation. When respondents were asked about the number of patients they had seen in their career who met their indications for hand transplantation, the average was approximately 1.35 patients per surgeon. The most accepted indications for hand transplantation were loss of bilateral hands (N ⫽ 366, 78%) followed by amputation of a dominant hand (N ⫽ 149, 32%) (Table 3). However, there was also support (N ⫽ 128, 27%) for hand transplantation in those patients who had failed multiple reconstructions (such as loss of toe-to-thumb). The majority of the surgeons did not feel that transplantation of the nondominant hand was an indication for hand transplantation, as evidenced by a low level of support (N ⫽ 66, 14% in favor of these transplants).
Hand Transplantation Is an Ethical Procedure if Performed on a Properly Selected Patient Strongly agree
Frequency
Percentage (%)
62
13%
Agree
272
58%
Disagree
105
22%
34
7%
Strongly disagree
Ethics in composite tissue allotransplantation Seventy-one percent (N ⫽ 335) believe that hand transplantation is an ethical procedure when performed on a properly selected patient (Table 4). Clinical cases for composite tissue allotransplantation In response to clinical situations mimicking past hand transplantations, 313 (66%) would offer transplantation to a bilateral hand amputee, whereas only 41 (9%) would offer transplantation to a patient with diabetes who had lost his or her dominant hand. DISCUSSION The traumatic amputation of a patient’s hand is a disfiguring event with immeasurable personal, psychological, financial, and social implications in addition to the obvious functional limitations. The ability to safely transplant a fully integrated and functional hand to these amputees would be of tremendous reconstructive value. Currently, clinical hand transplantation remains an experimental procedure, and the outcomes of this innovative procedure are still being determined. In the current era of immunosuppression, 41 hand transplantations have been performed on 30 patients. The results thus far have been promising, with most patients reporting varying degrees of return of function.3–5 The longest follow-up available is from the second hand transplant performed by the group in Louisville; the patient is now almost 9 years postoperative with a functioning hand.20 –22 In a recent article, the group in Louisville reported detailed outcomes of the first 2 American hand transplant recipients at 8 and 6 years post-transplantation. Both patients have allograft survival, with improvements in intrinsic muscle activity, total active motion, and return of functional grip, pinch strength, and sensibility. The latest Carroll test scores, which measure the patients’ ability to perform tasks requiring a combination of mobility, motor function, and sensation, are fair for patient 1 (72/99) and fair for patient 2 (55/99).
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These Carroll test scores exceed the expected results of 20 –30 of 99 that would be achieved with a prosthetic hand. The first patients’ Semmes-Weinstein monofilament sensation testing is in the normal range for all fingertips, and the patient has shown improvement in both static 2-point discrimination and moving 2-point discrimination over previous testing. Touch localization, stereognosis, and temperature and vibration sensation have also returned. The second patient has not demonstrated a similar return of sensation through year 6; however, in 2008, his protective sensation was noted to have returned.22 In 2003, the ASSH reviewed its position paper regarding hand transplantation. They concluded, based on the clinical experience of 14 patients, that hand transplantation should still be considered an experimental procedure that might enhance function or appearance in carefully selected patients. They proposed that additional research and progress in transplant immunology would be needed before hand transplantation could be considered a consistently safe and efficacious practice (www.hand-surg.org; ASSH Public Information. Hand Transplantation: Current Status). In this study, we sought to examine the current attitudes regarding the emerging field of hand transplantation from those who treat complex hand injuries. We also sought to assess the changes in attitudes that might have occurred due to the growing number of hand transplant cases and the increased length of follow-up. Although most hand surgeons can agree that tremendous potential benefits could be achieved from a successful hand transplantation, the surveyed membership remains hesitant to approve the practice. This skepticism is demonstrated by the fact that only 24% of the hand surgeons surveyed were in favor of hand transplantation. The majority of respondents were against hand transplantation (45%) or remained undecided (31%). Twenty respondents (4%) report changing their opinion about hand transplantation and now support transplantation. This may be due in part to their recognition of the relative success of recent hand transplantations. This suggests that hand transplantation could potentially attain more widespread acceptance over time, as additional outcome data regarding long-term functional results become available. Of the 474 members who responded to the survey, 353 (75%) replied that they currently perform microsurgical reconstruction of the hand in the form of digital replantation, hand replantation, or functional free tissue transfers (toe to thumb). A sub-analysis was performed to exclude the 121 members who no longer performed microsurgery
to see whether surgeons who treated complex hand injuries were more inclined to be in favor of hand transplantation. However, when the results were adjusted, the support for hand transplantation remained comparable, with 86 (24%) in favor of hand transplantation, 162 (46%) against hand transplantation, and 105 (30%) undecided. The predominant limiting factor to the clinical application of hand transplantation is the need for chronic immunosuppression. Long-term immunosuppression is associated with many potential adverse effects, including opportunistic infections, malignancies, and organ failure. In addition, all of the hand transplants have experienced episodes of acute rejection that required treatment.3,4,23–26 This might be a result of the relative increase in antigenicity over the more homogenous classic organ allografts due in part to the presence of multiple tissue types (especially the skin). These factors explain the limited support for transplanting hands (only 16% of respondents) with the currently available immunosuppressive regimens. The additional unknown datum is how long these transplants will last. The support for the current regimens would increase by 13% if current transplants were shown to be viable and functional after 10 years. A considerable group of surgeons (28%) stated that they would accept hand transplantation only if a more advanced and less toxic immunosuppressive regimen was developed. The largest group of surgeons (38%) wished to wait for the establishment of immunologic tolerance before proceeding with further transplants. Only 10% of surgeons stated that there was no indication for hand transplantation. A critical issue in terms of the application of hand transplantation in the reconstruction of complex hand injuries is what the accepted indications should be. An overwhelming majority of surgeons (71%) believe that hand transplantation is an ethical procedure when performed on a properly selected patient. This was especially true when they were asked about using hand transplantation to treat bilateral upper extremity amputees (78% in favor of transplantation). The support for other listed indications was not as strong, with only 32% in support of transplantation after amputation of a dominant hand and 27% in cases of multiple failed attempts at reconstruction. There was less support of transplantation to treat an amputated thumb (20%), multiple digits (17%), or a nondominant hand (14%). A small percentage (17%) again responded that there was no indication for hand transplantation. The continued uncertainty about hand transplantation might stem from the attitude shared by 69% of the
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hand surgeons regarding hand transplantation as a highrisk endeavor. These concerns are not unique to hand transplantation but are shared by other types of CTA, as the majority of respondents also perceived facial transplantation and abdominal wall transplantation as highrisk procedures. These concerns were reflected in the proposed clinical situations mimicking past hand transplantation cases, for which 66% offered transplantation to a bilateral hand amputee and only 9% to a patient with diabetes who had lost his or her dominant hand. Surveys are a useful tool for examining current attitudes and practice patterns of physicians. The 22% response rate achieved in our study likely reflects that a large percentage of those who were sent the survey do not perform complex hand microvascular reconstruction and thus did not respond. We sent out the most surveys (N ⫽ 2150) of any recently published ASSH survey and received 474 responses. Previous studies have had higher percentages of responses (28.7% to 45%), but the actual numbers of respondents varied from 280 to 591 surgeons.27–31 The fact that 474 hand surgeons responded to the study indicates that a considerable percentage of ASSH members found the issues addressed in the survey to be important. A limitation of the present study was the possibility of non-respondent bias. Hand surgeons not using their microsurgical training and not treating these types of complex hand injuries and amputations in their current practice may have been less inclined to respond to the survey. It is possible that the responses of these surgeons could have increased the number of those surgeons against hand transplantation. Such bias has been shown to be extremely difficult to prove.32 The results of this survey demonstrate support within the ASSH for continued clinical hand transplantation. This support was strongest for cases of bilateral hand amputation, in which patients have fewer available treatment options. The majority of hand surgeons continue to be wary of the effects of current immunosuppressive regimens and the risks of acute and chronic rejection. The wider application of hand transplantation appears to depend on the development of less toxic immunosuppressive protocols or a future method of tolerance induction. REFERENCES 1. Lee WPA, Yaremchuk MJ, Pan Y-C, Randolph MA, Tan CM, Weiland AJ. Relative antigenicity of components of a vascularized limb allograft. Plast Reconstr Surg 1991;87:401– 411. 2. LLULL R. An open proposal for clinical composite tissue allotransplantation. Transpl Proc 1998;30:2692–2696.
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3. Lanzetta M, Petruzzo P, Margreiter R, Dubernard JM, Schuind F, Breidenbach W, et al. The international registry on hand and composite tissue transplantation. Transplantation. 2005 May;79:1210 – 1214. 4. Lanzetta M, Petruzzo P, Dubernard JM, Margreiter R, Schuind F, Breidenbach W, et al. Second report (1998 –2006) of the international registry of hand and composite tissue transplantation. Transpl Immunol 2007;18:1– 6. 5. Ravindra KV, Wu S, Bozulic L, Xu H, Breidenbach WC, Ildstad ST. Composite tissue transplantation: a rapidly advancing field. Transplant Proc. 2008;40:1237–1248. 6. Birchall M. Human laryngeal allograft: shift of emphasis in transplantation. Lancet 1998;351:539 –540. 7. Strome M, Stein J, Esclamado R, Hicks D, Lorenz RR, Braun W, et al. Laryngeal transplantation and 40-month follow-up. N Engl J Med 2001;344:1676 –1679. 8. Birchall MA, Lorenz RR, Berke GS, Genden EM, Haughey BH, Siemionow M, et al. Laryngeal transplantation in 2005: a review. Am J Transplant 2006;6:20 –26. 9. Devauchelle B, Badet L, Lengelé B, Morelon E, Testelin S, Michallet M, et al. First human face allograft: early report. Lancet 2006; 368:203–209. 10. Dubernard JM, Lengelé B, Morelon E, Testelin S, Badet L, Moure C, et al. Outcomes 18 months after the first human partial face transplantation. N Engl J Med 2007;357:2451–2460. 11. Levi DM, Tzakis AG, Kato T, Madariaga J, Mittal NK, Nery J, et al. Transplantation of the abdominal wall. Lancet 2003;361:2173–2176. 12. Selvaggi G, Levi DM, Kato T, Madariaga J, Moon J, Nishida S, et al. Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation. Transplant Proc 2004;36:1561–1563. 13. Siegler M. Ethical issues in innovative surgery: should we attempt a cadaveric hand transplantation in a human subject? Transplant Proc 1998;30:2779 –2782. 14. Lee WP, Mathes DW. Hand transplantation: pertinent data and future outlook. J Hand Surg 1999;24A:906 –913. 15. Hatrick NC, Tonkin MA. Hand transplantation: a current perspective. ANZ J Surg 2001;71:245–251. 16. Cooney WP, Hentz VR. Hand transplantation—primum non nocere. J Hand Surg 2002;27A:165–168. 17. Breidenbach WC III, Tobin GR II, Gorantla VS, Gonzalez RN, Granger DK. A position statement in support of hand transplantation. J Hand Surg 2002;27A:760 –770. 18. Jones NF. Concerns about human hand transplantation in the 21st century. J Hand Surg 2002;27A:771–787. 19. Lees VC, McCabe SJ. The rationale for hand transplantation. Transplantation 2002;74:749 –753. 20. Jones JW, Gruber SA, Barker JH, Breidenbach WC. Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team. N Engl J Med 2000;343:468 – 473. 21. Tobin GR, Granger DK, Breidenbach WC. Hand transplantation follow-up. Lancet 2001;358:1018. 22. Breidenbach WC, Gonzales NR, Kaufman CL, Klapheke M, Tobin GR, Gorantla VS. Outcomes of the first 2 American hand transplants at 8 and 6 years posttransplant. J Hand Surg 2008;33A:1039 –1047. 23. Dubernard JM, Owen E, Herzberg G, Lanzetta M, Martin X, Kapila H, et al. Human hand allograft: report on first 6 months. Lancet 1999;3531:1315–1320. 24. Kanitakis J, Jullien D, Petruzzo P, Hakim N, Claudy A, Revillard JP, et al. Clinicopathologic features of graft rejection of the first human hand allograft. Transplantation 2003;76:688 – 693. 25. Lineaweaver WC. Chronic rejection, hand transplantation, and the monkey’s paw. Microsurgery 2006;26:419 – 420. 26. Horner BM, Randolph MA, Huang CA, Butler PE. Skin tolerance: in search of the Holy Grail. Transpl Int 2008;21:101–112. 27. McCarthy DM, Boardman ND III, Tramaglini DM, Sotereanos DG, Herndon JH. Clinical management of partially lacerated digital
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flexor tendons: a survey of hand surgeons. J Hand Surg 1995; 20A:273–275. 28. Alderman AK, Chung KC, Kim HM, Fox DA, Ubel PA. Effectiveness of rheumatoid hand surgery: contrasting perceptions of hand surgeons and rheumatologists. J Hand Surg 2003;28A:3–11. 29. Zarkadas PC, Gropper PT, White NJ, Perey BH. A survey of the surgical management of acute and chronic scapholunate instability. J Hand Surg 2004;29A:848 – 857.
30. Mallette P, Ring D. Attitudes of hand surgeons, hand surgery patients, and the general public regarding psychologic influences on illness. J Hand Surg 2006;31A:1362–1366. 31. Payatakes AH, Zagoreos NP, Fedorcik GG, Ruch DS, Levin LS. Current practice of microsurgery by members of the American Society for Surgery of the Hand. J Hand Surg 2007;32A:541–547. 32. Lau FH, Chung KC. Survey research: a primer for hand surgery. J Hand Surg 2005;30A:893–902.
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● ● ● ● ● ●
APPENDIX—SURVEY SENT TO ACTIVE MEMBERS OF THE ASSH Demographics 1) Please check the area(s) in which you are certi-
fied. 2) Please check the area(s) in which you are accred-
ited. 3) How many years have you been in practice? Practice profile 4) Approximately how many digital replantations
15)
do you perform per year? 5) Approximately how many hand replantations have
you performed in your career? 6) Approximately how many functional free tissue
16)
transfers (toe to thumb) for hand reconstruction do you perform per year? Composite tissue allotransplantation 7) Has your opinion regarding the use of composite
8) 9) 10) 11) 12)
13) 14)
tissue allotransplantation to reconstruct complex tissue loss (such as hand amputation) changed? ● Yes, Changed. I am now in favor of hand transplantation ● Yes, Changed. I am now against hand transplantation ● No, Not changed. I am still in favor of hand transplantation ● No, Not changed. I am still against hand transplantation ● Undecided What level of risk do you assess to a hand allotransplant? What level of risk do you assess to a free flap to the hand (toe to thumb transfer)? What level of risk do you assess to facial allotransplantation? What level of risk do you assess to an abdominal wall allotransplant? Clinical application of hand allotransplantationx ● Is acceptable with the current immunosuppression offered today ● Would only be acceptable if current transplants are shown to be viable at 10 years ● Would only be acceptable with a more advanced immunosuppressive regimen ● Would only be acceptable if immunologic tolerance to the graft could be achieved ● Is not justifiable Hand transplantation is an ethical procedure if performed on a properly selected patient. Indications for hand, partial hand, or digit allotransplantation should include:
17)
18)
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Amputation of thumb Amputation of multiple digits Amputation of non-dominant hand Amputation of dominant hand Amputation of bilateral hands Multiple failed reconstructions (e.g., failed toe to thumb) ● There is no acceptable indication for hand transplantation Based on your answers to the above questions, how many patients have you seen in your career that meet your indications for hand transplantation? How many of these patients would meet psychosocial requirements (ability to take immunosuppression, realistic goals, support system, ability to deal with complications, etc.) to undergo hand transplantation? Suppose you are the leader of a well-funded, multidisciplinary hand transplant team with IRB approval to conduct a hand transplantation. Please consider the following case presentations and advise on treatment options. Case 1—You are asked to see a 37-year-old man who lost his dominant left hand and lower forearm 13 years ago in a fireworks accident. He has a myoelectric prosthesis that allows him to work as a paramedic. Past medical history is remarkable for well-controlled type 1 diabetes mellitus for 11 years. The patient is a nonsmoker. He has no evidence of complications of diabetes. He is not satisfied with the functionality of his myoelectric prosthesis after extensive physical therapy and rehabilitation. He has heard about hand transplantation and wants to know if he would be a candidate. You inform him of the current knowledge of risks, benefits, and limitations of hand transplantation as an experimental procedure. You discuss other options for treatment, such as alternate prostheses. He has excellent comprehension of the discussion and desires hand transplantation. You recommend: ● Place the patient on the hand transplantation list. ● Encourage the patient to try a different prosthesis. ● Discourage the patient from further treatment. Case 2—You are asked to see a 31-year-old man who underwent bilateral hand amputation at the distal forearm 6 years ago after a fireworks accident. Although he has completed extensive rehabilitation with his prostheses, he cannot
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complete many activities of daily living. He is otherwise healthy and does not smoke. He has heard about bilateral hand transplantation and wants to know more. You inform him of the current knowledge of risks, benefits, and limitations of hand transplantation as an experimental procedure. You discuss other options for treatment, such as alternate prostheses. He
has excellent comprehension of the discussion and desires bilateral hand transplantation. You recommend: ● Place the patient on the hand transplantation list. ● Encourage the patient to try a different prosthesis. ● Discourage the patient from further treatment.
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