Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies

Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies

EDITOR’S CHOICE Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies Valeriy Shubinets, MD,* Christine McAndrew, MS,† Jaclyn Ma...

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EDITOR’S CHOICE

Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies Valeriy Shubinets, MD,* Christine McAndrew, MS,† Jaclyn Mauch, BA,* Alyssa Ricker Glennon, BS,‡ Stephen J. Kovach, MD,* Benjamin L. Gray, MD,† David R. Steinberg, MD,† David J. Bozentka, MD,† Laurent Lantieri, MD,§ Benjamin Chang, MD,* L. Scott Levin, MD,† Ines C. Lin, MD* As the field of vascularized composite allotransplantation continues to expand, new upper extremity transplant candidates are being considered. We recently evaluated a bilateral amputee who had a mid-forearm amputation and a contralateral metacarpal hand amputation. In the latter limb, a “partial” hand transplant that preserved the majority of the patient’s existing hand, including a partially severed thumb with intact thenar muscle function, was proposed. The feasibility of this partial hand transplant was studied in fresh-frozen cadaver limbs. This report details the proposed approach, the cadaveric dissections, and the lessons learned from these dissections. Issues of osteosynthesis, microvascular planning, and intrinsic muscle recovery are discussed, all of which are critical considerations for partial hand transplant candidates. Ultimately, the partial hand approach was felt to be inferior to a more conventional distal forearm transplant in this particular candidate. Practical, functional, and ethical implications of such decision are presented. (J Hand Surg Am. 2018;-(-):-e-. Copyright Ó 2018 by the American Society for Surgery of the Hand. All rights reserved.) Key words Allograft, hand, upper extremity, vascularized composite allotransplantation, VCA.

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remains the most common form of vascularized composite allotransplantation (VCA), with more than 120 transplants in 74 patients reported worldwide.1 Most often, UE transplants are performed at the level of the forearm, with osteosynthesis of radius and ulna routinely executed in a very efficient and precise manner.1,2 As the field of VCA continues to expand, new UE transplant candidates PPER EXTREMITY (UE) TRANSPLANTATION

From the *Department of Surgery, Division of Plastic Surgery; the †Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA; ‡Materialise, Plymouth, MI; and the §Department of Plastic, Aesthetic and Reconstructive Surgery, Hôpital Européen Georges Pompidou, Paris, France. Received for publication October 8, 2017; accepted in revised form April 24, 2018. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article. Corresponding author: Ines C. Lin, MD, Department of Surgery, Division of Plastic Surgery, University of Pennsylvania, 3400 Civic Center Blvd, Perelman Center for Advanced Medicine, South Pavilion, 14th Floor, Philadelphia, PA 19104; e-mail: ines.lin@uphs. upenn.edu. 0363-5023/18/---0001$36.00/0 https://doi.org/10.1016/j.jhsa.2018.04.031

are being considered. Our institution recently evaluated for bilateral UE transplantation a patient who had a right mid-forearm amputation and a left “partial” hand amputation. In the left UE, the second to fifth digits were amputated at the metacarpophalangeal joints and the thumb was severed at the proximal phalanx base (Fig. 1). The patient was able to adduct and oppose the shortened thumb, and strongly desired its preservation. Using fresh-frozen cadaver limbs, we aimed to assess the feasibility of a partial hand transplant in our candidate, focusing on anatomic and functional concerns of a metacarpallevel amputation with a partial thumb. This report describes the findings from these cadaveric dissections, including the obstacles encountered and the important lessons learned. CASE REPORT The candidate was a 42-year-old woman who sustained bilateral UE limb loss due to streptococcal sepsis several years earlier. In the right limb, a standard mid-forearm transplant approach was

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FIGURE 1: Preoperative evaluation of the transplant candidate’s left hand. A X-rays of the left hand. B 3D CAD-CAM reconstruction of the patient’s bony framework. C Photographs of the patient’s left hand.

FIGURE 2: Summary of the proposed partial hand transplant approach using a cadaveric left limb. A Recipient left cadaveric limb with the donor left partial hand. B Volar view of inlay of the donor and recipient hands. C Dorsal view of the donor and recipient hand planned coaptation.

FIGURE 3: Structure of cadaveric transplant rehearsals. Each rehearsal included 4 cadaveric limbs and 4 respectively assigned teams: (1) right donor, (2) right recipient, (3) left donor, and (4) left recipient. The right limb involved a standard mid-forearm transplant approach. The left limb involved the “partial hand” transplant approach. Each team worked separately at the beginning, with recipient and donor teams then joining together to simulate osteosynthesis, tendon repairs, and neurovascular anastomoses. The left partial hand transplant is the focus of this report. J Hand Surg Am.

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FIGURE 4: Design of A patient-specific osteotomies, B screw placement, and C bone cutting guides using CAD-CAM technology.

to augment the recipient thumb length (Fig. 2). Five rehearsals with 4 surgical teams, working simultaneously, and each led by a board-certified hand surgeon, were dedicated to evaluating this strategy (Fig. 3). Key observations from the left partial hand transplant dissections Osteosynthesis: Because the osteosynthesis involved 5 digits, several measures were taken to streamline this step. The thumb was stabilized via percutaneous pinning because the native proximal phalanx base was too short to achieve secure fixation with a plate and screws. In the other digits, initial plans for stepcut osteotomies with interfragmentary screw fixation were replaced with simple transverse osteotomies at mid-shaft of each metacarpal (Figs. 4, 5). With the aid of 3-dimensional computer-aided design and computer-aided manufacturing (CAD-CAM) technology, patient-specific bone cutting guides were used.3 Despite these measures, the osteosynthesis— and the required exposure—took on average an hour longer than the plating of radius and ulna on the contralateral side. Revascularization of the donor hand: Although osteosynthesis took place at the metacarpal level, the microvascular anastomoses were planned more proximally, at the wrist (Fig. 6). This strategy had the advantages of larger vessel caliber and the need for only 2 anastomoses: radial and ulnar vessels. Despite these advantages in theory, the following issues arose in practice. The donor palmar arches had to be “doubled” with the recipient arches, creating considerable bulk and complexity in the final product. Although preoperative computed tomography angiography failed to define vascular anatomy beyond the wrist, our suspicion was that the patient had at least an intact deep palmar arch.

FIGURE 5: Final stage of donor-recipient osteosynthesis using CAD-CAM technology planning.

considered. In the left, partial hand limb, the plan was to join the donor and recipient hands at the metacarpal shaft level, while transferring the distal donor thumb en bloc with the rest of the donor hand J Hand Surg Am.

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FIGURE 6: Photographs from cadaveric dissection sessions. A, B Dissection of the distal donor thumb. The donor thumb was to be transplanted en bloc with the rest of the donor hand. Its vascular supply was traced to the radial artery via the princeps pollicis artery or the superficial palmar arch via the first palmar metacarpal palmar artery (see Fig. 7), both of which proved to be very challenging. C Dissection of the donor palmar space. D, E Donor hand fully dissected (D—volar view; E—dorsal view). Note the flexor and extensor tendons, as well as the radial and ulnar arteries on each side. While osteosynthesis was planned at the metacarpal level, the microvascular anastomoses were planned more proximally at the wrist. F, G Donor and recipient hands before osteosynthesis (F—volar view; G—dorsal view). H Contralateral distal forearm transplant osteosynthesis for comparison.

Even if not, some arch remnant had to be present to perfuse the existing partial hand, which meant that fitting all components together at the end required an additional step. It also meant that the anastomoses had to be performed end-to-side, so that the remainder of the recipient hand maintained perfusion. From the donor perspective, ensuring thumb tip viability created an additional degree of difficulty. If the donor thumb tip were to be transplanted en bloc with the rest of the donor hand, its vascular supply had to be traced either to the radial artery via the princeps pollicis or to the superficial palmar arch (Fig. 7).4 In cadaver limbs, this dissection proved extremely tedious, time consuming, and not always reliable.

procedures. The extensive exposure also put the native thenar muscles at risk of denervation. Reconstructing the median nerve in the carpal tunnel was not possible because it jeopardized the recurrent branch, which meant that the common digital nerves had to be repaired individually instead—a task made more difficult by the scarring in the distal hand. Similarly, performing ulnar nerve coaptation at the wrist jeopardized the function of the adductor pollicis. DISCUSSION This report presents a unique case of a UE transplant candidate who was evaluated for a partial hand transplant. The majority of UE transplants to date have been performed at the forearm level.1 Transplants within the hand itself are rare. In the Chinese experience of 15 UE transplants in 12 patients, 1 patient had a palm transplantation and another patient a thumb transplantation.5 Limited operative details are available for either of these operations. Rampazzo et al6 recently described a cadaveric study to test the

Intrinsic function and nerve coaptations: Given the level of hand amputation, the patient’s intrinsic lumbrical and interossei muscles were likely fibrosed and functionless. The proposed transplant strategy at the diaphysis of the metacarpals would not restore their function, and without their recovery, the patient would probably require future anti-clawing J Hand Surg Am.

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however, were not the only reason to question the partial hand approach. One could simplify the approach, for example, by not reconstructing the thumb and avoid the tedious, sometimes unreliable, dissection. Such compromise would improve grip, but leave the patient with insufficient thumb length for pinch and opposition. Even under these simplified technical circumstances, we struggled with a good strategy for restoring the lumbrical-interossei muscle function that would allow for a more functional composite grip. In contrast, the distal forearm transplant offers a reasonably high likelihood of intrinsic recovery, supported by our experience and that of others.1,8,9 In this candidate, specifically, nerve endings and coaptations are more distal than in a transradial amputee, further improving the likelihood of success. Overall, when VCA operations are performed in a safe and ethical way, with meticulous preparation and follow-up, successful outcomes can be achieved. Although there are no guarantees, the field has advanced tremendously. Just 20 years ago, it was debated whether hand transplantation should even be attempted in a patient.10 Today, we are beginning to hold these operations to a certain standard and some results are almost expected, not just hoped for.11 Other reconstructive options for the partial hand amputation include toe transfers. Our patient has a type IIA metacarpal hand, which can be classically reconstructed with a trimmed great toe for the thumb and a combined second and third toe transfer for the fingers.12 The value of such transfers would be debatable if the patient were also to receive a forearm transplant in the contralateral limb, already exposing her to risks of immunosuppression. Toe transfers would lead to donor-site morbidity and likely a result functionally inferior to the distal forearm transplant. Another alternative is to develop a creative myoelectric prosthetic device that can specifically take advantage of the patient’s unique anatomy based on the recent advances in targeted muscle reinnervation. An obvious disadvantage to the distal forearm transplant strategy is loss of the native partial hand and thumb. Even if the hand lacks full function, the patient’s emotional attachment to it cannot be underestimated. Choosing to have the hand amputated and undergoing a distal forearm transplant is a difficult decision, with significant ethical considerations. Much has been written about the ethical dilemmas in VCA.13,14 In contrast to solid organ transplantation, VCA does not prolong life and instead, likely shortens it due to sequelae of

FIGURE 7: Blood supply to the thumb, as viewed from the volar side. The thumb’s blood supply consists of the princeps pollicis artery (PPA) and the first palmar metacarpal artery (1MCA).4 If the donor distal thumb were to be transplanted en bloc with the rest of the donor hand, its blood supply had to rely either on the PPA (down to the radial artery) or the 1MCA (to the superficial palmar arch). Note that the dorsal blood supply to the thumb is not shown, which consists of the dorsal ulnar digital artery and dorsal radial digital artery, arising from the PPA and the 1MCA, similar to the volar blood supply.

feasibility of multidigit transplantation for reconstruction of a metacarpal hand. Although there are some similarities to our study, their osteosynthesis was performed at the level of proximal phalanges with preservation of recipient metacarpophalangeal joints and lumbrical-interossei muscles.6 Iglesias et al7 performed a cadaveric study to test the feasibility of a partial hand transplant for patients with rheumatoid arthritis; their approach, however, involved only transfer of the musculoskeletal components, with preservation of recipient skin and osteosynthesis at the distal forearm. Based on the lessons learned from our cadaveric dissections, a collective decision among team members was made that amputation of the partial hand for a distal forearm transplant is a better option for the patient than the partial hand approach. Distal forearm-level transplantation has the benefits of (1) fewer sites of osteosynthesis, (2) end-to-end microvascular anastomoses at the wrist, without concern for perfusion of the remaining hand or donor thumb, (3) fewer and more straightforward nerve coaptations away from areas of scar, and (4) high likelihood of lumbrical-interossei recovery (Table 1). Based on our team’s prior experience, if a bilateral forearm-based transplant takes 10e12 hours, execution of a partial hand transplant would add at least 3 more hours. The added time and complexity, J Hand Surg Am.

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TABLE 1.

Comparison of Partial Hand and Distal Forearm Transplant Strategies for the Patient Discussed Partial Hand

Five-bone osteosynthesis

Factors

Distal Forearm

Osteosynthesis

Smaller, more intricate bones and hardware End-to-side, at the wrist Need for preservation of recipient partial hand perfusion

Two-bone osteosynthesis (radius and ulna) Larger bones and hardware

Microvascular anastomoses

End-to-end, at the wrist No concern for remaining recipient partial hand perfusion

“Doubling” of arches/arch remnants

No “doubling” of arches/arch remnants

Tedious dissection to preserve distal donor thumb blood supply

No concern for distal donor thumb perfusion

Multiple, at a common digital nerve level

Nerve coaptations

Fewer, at the wrist level

Dissection and preservation of the recurrent branch of the median nerve

No concern for remaining thenar muscle innervation

Dissection and preservation of the ulnar nerve branch to the adductor pollicis

No concern for remaining adductor pollicis innervation

Dissection of nerves in areas of the scar

Dissection of nerves away from the scar

Preservation of the existing native hand and thumb

Functional endresult

Amputation of the existing native hand and thumb

Nerve regeneration starts distal to thenar muscles

Nerve regeneration starts more proximally

Absence of lumbrical-interossei muscle function

Reasonable chance of intrinsic recovery given low median and ulnar nerve coaptations

Standard VCA decision-making process and ethical considerations

Ethical considerations

Added degree of decision making and ethical calculation due to native hand amputation

Multiple scars in the hand

Aesthetic concerns

Scars in the distal forearm (can be hidden in long-sleeve clothes)

Technical, functional, and ethical factors are presented. If a particular factor is thought to be a relative advantage, it is italicized. VCA, vascularized composite allotransplantation.

immunosuppression. A trade-off between quantity and quality of life is made. It has been concluded that VCA is an ethically appropriate choice, but presents a very unique set of challenges when it comes to adequately informing the patient, respecting autonomy, and obtaining consent.13,14 In our patient, in particular, an extra level of ethical calculus exists with giving up the native partial hand. If successful, the transplanted hand will have all 5 extrinsically active digits, protective sensation, and a reasonable chance for intrinsic recovery—a result that is far better than the patient’s current hand and one we could not achieve with a partial hand strategy. Less important, but still worth noting, the scars in the distal forearm can be better camouflaged under long-sleeve clothes compared with multiple scars in the palm. There is an issue of greater antigenic load with shifting the transplant level proximally, but its significance has not been J Hand Surg Am.

clearly established. In fact, some have made an argument that the host rejection response may diminish in the setting of greater antigenic load, possibly through induction of chimerism.15,16 Ultimately, the patient has to make a choice to pursue the transplant or not. To help her, she will be given ample time to decide, her autonomy will be honored, and she will be provided with the necessary guidance and education to stay as informed as possible. The decision she makes may be the most difficult one in her life. Evaluated by a psychiatrist initially as part of the multidisciplinary VCA approach, the patient has not yet requested additional psychiatric or psychological counseling after being presented with a plan for the distal forearm transplant. These and other resources are available to the patient as needed. Notably, VCA operations at our institution have to be approved by the institutional review board. r

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In summary, this report presents the anatomic study of a partial hand transplant, including the obstacles and lessons learned from cadaveric dissections. Ultimately, the partial hand transplant approach in our candidate was concluded to be inferior to the distal forearm transplant. These lessons could be relevant to future partial hand transplant candidates.

7. Iglesias M, Butron P, Santander-Flores S, et al. Surgical technique in cadaveric donors for partial hand allotransplant in patients with rheumatoid arthritis. Transpl P. 2010;42(6):2389e2394. 8. Elliott RM, Tintle SM, Levin LS. Upper extremity transplantation: current concepts and challenges in an emerging field. Curr Rev Musculoskelet Med. 2014;7(1):83e88. 9. Petruzzo P, Lanzetta M, Dubernard JM, et al. The international registry on hand and composite tissue transplantation. Transplantation. 2010;90(12):1590e1594. 10. Siegler M. Ethical issues in innovative surgery: should we attempt a cadaveric hand transplantation in a human subject? Transplant Proc. 1998;30(6):2779e2782. 11. Breidenbach WC, Meister EA, Turker T, Becker GW, Gorantla VS, Levin LS. A methodology for determining standard of care status for a new surgical procedure: hand transplantation. Plast Reconstr Surg. 2016;137(1):367e373. 12. Wei FC, el-Gammal TA, Lin CH, Chuang CC, Chen HC, Chen SH. Metacarpal hand: classification and guidelines for microsurgical reconstruction with toe transfers. Plast Reconstr Surg. 1997;99(1): 122e128. 13. Caplan A, Purves D. A quiet revolution in organ transplant ethics. J Med Ethics. 2017;43(11):797e800. 14. Dumont M, Sann L, Gazarian A. Bilateral hand transplantation: supporting the patient’s choice. J Plast Reconstr Aesthet Surg. 2017;70(2):147e151. 15. Zhong R, He G, Sakai Y, et al. Combined small bowel and liver transplantation in the rat: possible role of the liver in preventing intestinal allograft rejection. Transplantation. 1991;52(3):550e552. 16. Nasir S, Bozkurt M, Krokowicz L, Klimczak A, Siemionow M. Correlation of chimerism with graft size and revascularization in vascularized and nonvascularized skin allografts. Ann Plast Surg. 2009;62(4):430e438.

REFERENCES 1. Shores JT, Malek V, Lee WPA, Brandacher G. Outcomes after hand and upper extremity transplantation. J Mater Sci Mater Med. 2017;28(5):72. 2. Haddock NT, Chang B, Bozentka DJ, Steinberg DR, Levin LS. Technical implications in proximal forearm transplantation. Tech Hand Up Extrem Surg. 2013;17(4):228e231. 3. Momeni A, Chang B, Levin LS. Technology and vascularized composite allotransplantation (VCA)-lessons learned from the first bilateral pediatric hand transplant. J Mater Sci Mater Med. 2016;27(11):161. 4. Ramirez AR, Gonzalez SM. Arteries of the thumb: description of anatomical variations and review of the literature. Plast Reconstr Surg. 2012;129(3):468ee476e. 5. Pei GX, Xiang DY, Gu LQ, et al. A report of 15 hand allotransplantations in 12 patients and their outcomes in China. Transplantation. 2012;94(10):1052e1059. 6. Rampazzo A, Kutz JE, Kaufman C, et al. A cadaver study of the feasibility of multidigit allotransplantation for reconstruction of the metacarpal hand. Plast Reconstr Surg. 2015;136(3):531e540.

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