Designing and utilizing 3D-printed skin incision guides during the first Dutch bilateral hand-arm transplantation.

OBJECTIVE: To preoperatively plan skin incision in the case of the first Dutch bilateral hand-arm transplantation. BACKGROUND: A bilateral hand-arm transplantation has been performed for the first time in the Netherlands in 2019. In the context of preparation for this surgical procedure, the optimal patient-specific skin flap was determined. Skin flaps should be properly matched between donor and recipient to ensure sufficient tissue for the approximation of skin over the tendon anastomosis, adequate distal tip perfusion, and esthetics. METHODS: Preoperatively, stereophotogrammetry was obtained from the upper extremities of the patient and a volunteer with similar body physique. Skin flap dimensions were determined for each extremity, which resulted in patient-specific incision patterns. Combining this digital information yielded practical skin incision guides for both the donor and acceptor arms. Finally, the computer-aided designs were 3D printed. RESULTS: The 3D prints were convenient to utilize in both shaping the donor flaps as in preparing the acceptor extremities, taking only a few seconds during precious ischemia time. There was sufficient skin flap perfusion, and the wound-healing followed an uncomplicated course. No corrections were made to the initial skin incisions. CONCLUSIONS: Three-dimensional printed templates were successfully utilized in the first Dutch bilateral hand-arm transplantation. We believe its usage increased time efficiency, improved the match of skin flaps in donor and recipient arms, and allowed us to control the amount of skin surplus without skin flap tip necrosis. In these procedures where time is of the essence, we believe preoperative planning is imperative for its success.

Unique Techniques or Approaches in Microvascular and Microlymphatic Surgery.

Several methods can be used for identifying tissues for transfer in donor-site-depleted patients. A fillet flap can be temporarily stored in other parts of the body and transferred back to the site of tissue defect, including covering the amputated stump of the lower extremity. Human arm transplant is rare and has some unique concerns for the surgery and postsurgical treatment. Cosmetics of the narrow neck of transferred second toes can be improved with insertion of a flap. Lymphedema of the breast after cancer treatment can be diagnosed with several currently available imaging techniques and treated surgically with lymphaticovenous anastomosis.

Trauma-induced Rejection in Vascularized Composite Allotransplantation.

: Vascularized composite allotransplantation (VCA) is a relatively new field in reconstructive medicine. Likely a result of the unique tissue composition of these allografts-including skin and often a bone marrow component-the immunology and rejection patterns do not always mimic those of the well-studied solid organ transplantations. While the number and type of VCAs performed is rapidly expanding, there is still much to be discovered and understood in the field. With more patients, new findings and patterns emerge and add to our understanding of VCA. Here, we present a case report of an upper extremity transplant recipient with trauma-induced rejection.

From Auto- to Allotransplantation: Immunomodulatory Protocol for Hand and Arm Transplantation.

AIM: To achieve a favorable risk-benefit balance for hand transplantation, an immunomodulatory protocol was developed in the laboratory and translated to clinical application. METHODS: Following donor bone marrow infusion into transplant recipients, hand and arm allografts have been maintained on low-dose tacrolimus monotherapy. RESULTS: Good-to-excellent functional recovery has been achieved in patients compliant with medication and therapy, thus restoring autonomous and productive lives. CONCLUSION: The risk-benefit balance can be tilted in favor of the hand transplant recipients by using an immunomodulatory protocol with minimum immunosuppression.

Decoupling between the hand territory and the default mode network after bilateral arm transplantation: four-year follow-up case study.

Several studies have suggested both a local and network reorganization of the sensorimotor system following amputation. Transplantation of a new limb results in a new shifting of cortical activity in the local territory of the transplanted limb. However, there is a lack of information about the reversibility of the abnormalities at the network level. The objective of this study was to characterize the functional connectivity changes between the cortical territory of the new hand and two intrinsic network of interest: the sensorimotor network (SMN) and the default mode network (DMN) of one patient whom received bilateral forearm transplants. Using resting-state fMRI these two networks were identified across four different time points, starting four months after the transplantation surgery and during three consecutive years while the patient underwent physical rehabilitation. The topology of the SMN was disrupted at the first acquisition and over the years returned to its canonical pattern. Analysis of the DMN showed the normal topology with no significant changes across acquisitions. Functional connectivity between the missing hand's cortical territory and the SMN increased over time. Accordingly, functional connectivity between the missing hand's cortical territory and the DMN became anticorrelated over time. Our results suggest that after transplantation a new reorganization occurs at the network level, supporting the idea that extreme behavioral changes can affect not only the local rewiring but also the intrinsic network organization in neurologically healthy subjects. Overall this study provides new insight on the complex dynamics of brain organization.

Experience With Patient Referrals for Upper Extremity Transplantation at a U.S. Academic Medical Center.

PURPOSE: To date, there have been over 100 upper extremity transplantations (UET) performed worldwide. However, little data are available regarding institutional screening practices or description of the population of patients that seek transplantation as a treatment modality for their upper extremity disabilities. We performed a review of our institutional experience in an attempt to better understand our referral patterns and identify factors that may be associated with successful screening. METHODS: Contact demographic data, injury characteristics, and mode of referral were retrospectively reviewed from 2010 through 2015. Differences in demographic data, injury-related characteristics, and clinical trial outcomes were assessed with the Chi-square test or Fisher exact test. RESULTS: There were a total of 89 UET contacts. The average age was 35.2 years, with most contacts being white (n = 24). The majority were male (n = 66; 75.0%) and the most common indication for referral was trauma (n = 43; 55.8%). Of the 89 contacts, 20 (22.5%) were physician referrals and 69 (77.5%) were self-referrals. Physician referrals led to the most screened and accepted contacts, whereas self-referrals more often led to immediate exclusion. CONCLUSIONS: This study gives an overview of the demographic composition of our UET contacts, with a specific emphasis on mode of referral. We have identified that physician referrals have led to more screened and accepted patients versus self-referred individuals. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

The First Hand Allotransplantation in Taiwan: A Report at 9 Months.

PURPOSE: Hand transplantations have been initiated and have been encouraged by promising results for more than 1 decade. The aim of this study was to present the first case of hand transplantation performed in Taiwan. MATERIALS AND METHODS: On September 3, 2014, we transplanted the left distal forearm and hand of a brain-dead managed 37 years to a man aged 45 years who had traumatic amputation of the distal third of his right forearm 30 years ago. The total ischemic time during the transplantation was 6 hours and 45 minutes. Immunosuppression included anti-thymocyte globulins, and methylprednisolone (Solumedrol) was used for the induction. Maintenance therapy included systemic tacrolimus, mycophenolic acid [mycophenolate mofetil (MMF)], and prednisone. A combination of systemic (tacrolimus/MMF/prednisolone) and topical immunosuppressant cream (clobetasol and tacrolimus) was applied if acute rejection occurred. Follow-up included routine posttransplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. RESULTS: The initial postoperative course was uneventful. No surgical complications were observed. Immunosuppression was well tolerated using tacrolimus, MMF, and prednisone, except for some immune-related complications. One episode of mild clinical and histological signs of cutaneous rejection was seen at 105 days after surgery. These signs disappeared after pulse therapy with Solumedrol and the topical application of immunosuppressive creams (tacrolimus and clobetasol). One infection episode occurred due to local cellulitis and axillary lymphadenopathy on day 140 and was successfully treated with antibiotics. The patient developed cytomegalovirus infection at 7 months that responded to medication. Intensive physiotherapy led to satisfactory progress in motor functioning. Sensory progress (Tinel sign) was good and reached the wrist by 3 months for the median and ulnar nerves, and could be felt in the finger tip by 9 months in response to deep pressure and light touch sensations. The patient has a lateral pinch that allows him to pick up and grip objects during daily living, although his muscle power is still insufficient. CONCLUSIONS: Hand allotransplantation is technically feasible. Currently available immunosuppression methods seem to control vascularized composite tissue allotransplantation rejection. A combination of topical and systemic immunosuppressants is a useful method to prevent acute hand allotransplant rejection.

The Physical and Psychosocial Benefits of Upper-Limb Transplantation: A Case Series of 5 Polish Patients.

BACKGROUND: Although upper-limb transplantation is not a life-saving procedure, every year more and more patients are ready to undergo this surgery. Conventional methods of treatment performed earlier have not brought the expected functional and aesthetic results. Patients who have received upper-limb transplantation (HTx) enjoy, in addition to the physical benefits associated with good functional effect, numerous benefits of a psychological and social nature. Investigation of these benefits was the aim of this interdisciplinary research. CASE REPORT: The wide spectrum of physical, psychological, and social benefits derived by recipients of limb transplantation include: improved physical fitness, recovery of the complete body form, corporeal well-being, enhanced self-esteem, recovery of self-confidence, a stable feeling of personal and social identity, higher integration of the body with performed social roles, greater confidence in the ability to act and have control over life, a feeling of greater security, the ability to return to work, restoration of social position, and positive personality changes. CONCLUSIONS: Potential benefits which may be derived by future upper limb recipients are manifested in the good functional effect of the transplantation, enhanced life satisfaction, and better functioning in society. It does not mean, however, restoration of 100% of fitness or absolutely problem-free functioning in everyday life, which is extremely important in the context of prevention of possible disappointment to future limb recipients.

Hand and upper extremity transplantation: an update of outcomes in the worldwide experience.

BACKGROUND: Hand/upper extremity transplantation is the most common form of vascularized composite allotransplantation performed to date. An Update of worldwide outcomes is reported. METHODS: The authors summarize the international experience with 107 known transplanted hand/upper extremities in 72 patients. Data from published medical literature, national and international meetings, lay press reports, and personal communications were utilized to provide the most up-to-date summary. RESULTS: Although 24 losses (including four mortalities) are known, three of the four reported mortalities and eight of 24 limb losses were caused by multiple type vascularized composite allotransplantations (combined upper and lower limb or upper limb and face). Seven more losses were attributable to 15 patients in the early experience in China. In the United States and Western Europe, only three other non-acute graft losses have been reported, resulting in a patient survival rate for unilateral or bilateral hand transplantation in isolation of 98.5 percent and an overall graft survival rate of 83.1 percent. CONCLUSIONS: Published functional outcomes continue to demonstrate improvement in function and quality of life. The international experience supports the idea that, for properly selected individuals, hand and upper extremity transplantation should be considered an important treatment option.

Forearm transplantation osteosynthesis using modified ulnar shortening osteotomy technique.

One of the challenges of forearm-level hand transplantation surgery is the achievement of osseous union of the ulna given the substantial soft tissue dissection, the use of immune modulating medications, and the diaphyseal level of osseous coaptation. Modification of the conventional surgical technique for an elective ulnar shortening osteotomy provides the advantages of precise osteotomy alignment, a large contact surface oblique osteotomy, and lag screw and compression plating technique. A step-by-step description of the developed modification is provided with a case example.

Technical implications in proximal forearm transplantation.

The field of vascularized composite allotransplantation has developed for more than a decade. Investigators are defining patient selection criteria, transplant indications, immunologic regimens, and tolerance. The majority of the current reported hand transplantations have been for treatment of distal forearm or hand amputations. In more proximal amputees, the functional outcome of the transplanted arm has some unique variables that require a different surgical approach. We present a single case of bilateral proximal forearm transplantation in effort to describe the unique technical considerations in this complex procedure. The surgical procedure is described in detail. At 19 months, our patient had 4/5 strength of finger and thumb flexors and protective extensor as well as 4/5 wrist flexors and extensors. Our patient had recovery of sensation. Our patient now lives independently and does her lower extremity prosthesis independently using her hands. These results are expected to continue to improve with more time. In hand transplantation, functional results have been very promising. The described approach of forearm transplantation allows the transfer of the entire functional unit, which should optimize the ultimate outcome for these more proximal injuries.

Procurement of hand and arm allografts.

Upper extremity transplantation has been at the forefront of vascularized composite allotransplantation. There have been more hand and upper extremity transplants than any other kinds of vascularized composite allotransplantation. However, it is a new and evolving field. Reconstructive surgeons are relative newcomers to the field of transplantation, and the procurement of upper extremity allografts has many subtleties that will differ depending on the intended recipient. However, there are certain principles that can be adhered to that this review serves to elucidate.

Above-elbow (supracondylar) arm transplantation: clinical considerations and surgical technique.

Vascularized composite allotransplantation, also known as "Reconstructive Transplantation" is becoming more commonplace worldwide. Hand and upper extremity transplantation make up the majority of clinical vascularized composite allotransplantation cases performed so far. As success with reconstructive transplantation becomes more common, more challenging examples of limb loss are being addressed, including above-elbow, or "supracondylar" upper extremity transplants. Although very few of these cases have been performed worldwide, the authors' experience includes the only 2 cases performed in the United States at the time of this report. This article will discuss indications, challenges, surgical technique, expected outcomes, and alternative technologies for treatment of limb loss above the elbow.

The case for lower extremity allotransplantation.

BACKGROUND: Despite generally excellent success with vascularized composite allotransplantation at many body sites over the past two decades, vascularized composite allotransplantation as a treatment modality for lower extremity amputees has not yet been fully embraced. METHODS: The authors summarize the anticipated benefits of lower limb allotransplantation, and reference the likely controversies relevant to this restorative therapeutic modality. RESULT: Based on evidence culled from both upper extremity and lower extremity transplant experience to date, the authors posit that allotransplantation for lower limb amputees may be a reasonable pursuit. CONCLUSION: The authors advocate for the renewed consideration of lower extremity allotransplantation.

Anesthetic management in upper extremity transplantation: the Pittsburgh experience.

BACKGROUND: Hand/forearm/arm transplants are vascularized composite allografts, which, unlike solid organs, are composed of multiple tissues including skin, muscle, tendons, vessels, nerves, lymph nodes, bone, and bone marrow. Over the past decade, 26 upper extremity transplantations were performed in the United States. The University of Pittsburgh Medical Center has the largest single center experience with 8 hand/forearm transplantations performed in 5 recipients between January 2008 and September 2010. Anesthetic management in the emerging field of upper extremity transplants must address protocol and procedure-specific considerations related to the role of regional blocks, effects of immunosuppressive drugs during transplant surgery, fluid and hemodynamic management in the microsurgical setting, and rigorous intraoperative monitoring during these often protracted procedures. METHODS: For the first time, we outline salient aspects of upper extremity transplant anesthesia based on our experience with 5 patients. We highlight the importance of minimizing intraoperative vasopressors and improving fluid management and blood product use. RESULTS: Our approach reduced the incidence of perioperative bleeding requiring re-exploration or hemostasis and shortened in-hospital and intensive care unit stay. Functional, immunologic and graft survival outcomes have been highly encouraging in all patients. CONCLUSIONS: Further experience is required for validation or standardization of specific anesthetic protocols. Meanwhile, our recommendations are intended as pertinent guidelines for centers performing these novel procedures.

The Spanish experience with hand, forearm, and arm transplantation.

This article summarizes the findings from 3 recipients of hand allografts, including a description of the preparatory surgery and the transplant and secondary procedures to enhance the function of the hand, forearm, and arm allografts. The study focuses on the complications and disability reported by each patient, with a minimum follow-up of 2 years. The few complications were controlled successfully with medical treatment. Hand transplantation is a major reconstructive procedure that requires careful medical follow-up. The authors provide the first report of a significant improvement in disabilities of the upper limb as a result of hand allotransplantation.

Achievements and challenges in composite tissue allotransplantation.

Overall, more than 60 hand/forearm/arm transplantations and 16 face transplantations have been performed in the past 12 years. In the European experience summarized here, three grafts have been lost in response to a vascular thrombosis (n = 1), rejection and incompliance with immunosuppression (n = 1) and death (n = 1). The overall functional and esthetic outcome is very satisfactory, but serious side effects and complications related to immunosuppression are challenges hindering progress in this field. The high levels of immunosuppression, skin rejection, nerve regeneration, donor legislation and the acceptance level need to be addressed to promote growth of this promising new field in transplantation and reconstructive surgery.

Preexpanded pedicle medial arm flap: an alternative method of massive facial defect reconstruction.

BACKGROUND: This article aims to describe the application of the preexpanded pedicle medial arm flap in facial reconstruction and the authors' experiences solving the problems that appeared during the whole reconstruction procedure. METHODS: A tissue expander was placed in the medial arm region and serially inflated for approximately 3 months. Then, the preexpanded flap was prepared as a tube flap and transferred to the face. The pedicle was divided 3 weeks later, and the flap was used to resurface the facial defect. RESULTS: Since 2005, the preexpanded pedicle medial arm flap has been used in face reconstruction for 9 patients ranging in age from 9 to 31 years. There were no perioperative complications or flap loss. The donor sites all were closed directly. In the authors' experience, a flap as large as 10 × 20 cm could be raised and safely transferred without flap necrosis. CONCLUSION: The results indicate that the application of the preexpanded pedicle medial arm flap can be one option for reconstruction of massive facial defects.

Bilateral trans-humeral arm transplantation: result at 2 years.

Unilateral and bilateral hand transplantations have been performed worldwide with good mid-term functional results. An above-elbow bilateral transplantation was performed in a 29-year-old male patient from a fully HLA-mismatched donor. Alemtuzumab induction and steroid-free maintenance immunosuppression with tacrolimus and mycophenolate was used. Due to acute rejection, steroids were introduced at 6 months. Three acute rejection episodes occurred, one treated with alemtuzumab. New-onset diabetes after transplant, dyslipemia and worsening of previous high blood pressure required treatment. At 26 months post-transplantation, the patient has excellent elbow active movement, active flexion and extension of the thumb and fingers, useful sensation and a gainful job. Based on the functional results of the case reported, bilateral trans-humeral transplantation could be a viable treatment for selected bilateral above-elbow amputees.

Composite tissue allotransplantation in Europe. Logistics and infrastructure of a centre.

BACKGROUND: Composite Tissue Allotransplantation (CTA) is a new medical field of growing importance. This paper focuses on the infrastructure and organisation of European CTA centres and discusses the differences between national health systems. MATERIAL/METHODS: Eight European centres (Valencia, Innsbruck, Munich, Lyon, Amiens, Creteil, Wroclaw, Monza) were sent with a specially-designed, standardized, 20-item questionnaire. RESULTS: Five of the eight centres returned our questionnaire: Munich, Innsbruck, Lyon, Amiens, Wroclaw. Since 1998, CTA has been performed at these centres. In both French centres and the Polish centre public funding is available in addition to the coverage provided by health insurers. In Munich the costs for a double upper-arm transplantation were Euro 150,000 with an additional Euro 50,000-70,000 per year. In Lyon the costs for a singular hand transplantation were Euro 70,000 per year and in Wroclaw (Poland) the costs for a hand or upper arm transplantation were Euro 20,000-30,000. As many as 17 different medical professions are involved in the CTA at the different centres. CONCLUSIONS: CTA is an innovative promising therapeutic tool that is based on the experiences of solid organ transplantation and profound microsurgical skills. Due to the complexity of the infrastructure, sourcing and the organisation CTA can only be successfully performed at specialized centres. A European network with an international European waiting list and a central coordination for CTA should be established. In order to advance CTA as an important tool in reconstructive surgery we must turn our attention to how the costs will be met, the legal environment for procurement of adequate donors and open ethical questions.