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Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 11  |  Issue : 4  |  Page : 184-192

Orthoplastic extremity reconstruction – From replantation to transplantation


Division of Plastic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

Date of Web Publication9-Nov-2018

Correspondence Address:
Prof. Lawrence Scott Levin
Department of Orthopaedic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/HMJ.HMJ_86_18

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  Abstract 


For more than a half century, the use of the operating microscope for extremity surgery has led to remarkable advances in the management of orthopaedic trauma, tumours, infections and congenital differences. The microsurgical reconstructive ladder ascends from basic microsurgical procedures such as digital artery or nerve repair, to more complex procedures such as autologous tissue transplantation (free tissue transfer). Tissue transfers have also become more sophisticated with the evolution from simple myocutaneous flaps to perforator-based flaps. Functional muscle transfers, toe-to-hand transfers, and recently vascularised composite allotransplantation make up the highest rungs on this ladder. The development of the orthoplastic approach simultaneously integrates principles and practices of both orthopaedic surgery and plastic surgery for optimal care of extremities based heavily on the application of microsurgical techniques. We will describe our contributions and innovations in orthopaedic clinical practice using microsurgical techniques as well as highlight our clinical, anatomic and basic science research in reconstructive microsurgery that have led to improvements in limb salvage, reconstruction and restoration during the last 25 years.

Keywords: Microsurgery, microsurgical techniques, orthopedic surgery, plastic surgery, reconstruction


How to cite this article:
Levin LS. Orthoplastic extremity reconstruction – From replantation to transplantation. Hamdan Med J 2018;11:184-92

How to cite this URL:
Levin LS. Orthoplastic extremity reconstruction – From replantation to transplantation. Hamdan Med J [serial online] 2018 [cited 2019 Nov 12];11:184-92. Available from: http://www.hamdanjournal.org/text.asp?2018/11/4/184/245140




  Early History Top


For more than a half century, the operating microscope has contributed to remarkable advances in extremity reconstruction. Dr. Julius Jacobsen introduced the use of the operating microscope for small vessel anastomosis in 1960, and a few years later, these techniques were first applied to surgery of the hand by Harold Kleinert in 1963. The first thumb replantation was subsequently reported by the Japanese orthopaedic surgeon Susumu Tamai in 1968. The clinical experience and influence of early microsurgical pioneers from the Far East such as Tamai (Japan) and Zhong Wei Chen (China) influenced other surgeons throughout the world to incorporate microvascular surgery into their practices. The author's first exposure and interest in microsurgery began in 1974, which was the time when many American centres were gaining experience with replantation and microneural repair.


  Replantation Top


Early reports of functional outcomes in digital replantation included our observations that correlated neural recovery with vascular patency; demonstrating improved sensibility in those replanted digits that has patent digital vessels on clinical follow-up.[1] Alternatives to replantation, such as the use of digital prosthesis were evaluated in an attempt to determine digital prosthetic use of those patients that had failed replantation.[2] We found that daily prosthetic use was poor and concluded that despite the large expenditure for digital prosthetics, patient satisfaction was also poor. Our description of heterotopic digital replantation demonstrated methods optimising hand function without replantation of all severed digits.[3] We developed an algorithm for alternatives to thumb replantation and described surgical techniques that included toe to hand transfers, index finger pollicisation and distraction lengthening of the metacarpal ultimately producing a functional hand with an opposable digit despite thumb replantation failure.[4],[5]

Over the last two decades, there has been a gradual shift from orthopaedic surgeons performing complex microsurgery such as microvascular tissue transfer (as was common in the 1970's) to plastic surgeons predominately performing microsurgical tissue transfers.[6] At this time, orthopaedic hand and microvascular fellowships may or may not prepare fellows adequately to perform the full spectrum of reconstructive microsurgery including revascularisation, replantation and complex free tissue transfer which are vitally important to optimise limb salvage and functional outcomes in a variety of upper and lower extremity conditions [Figure 1]. Our publication in 2007 outlined the diminution of American Society for Surgery of the Hand (ASSH) members performing replantation and elective microsurgery and substantiated claims made by the 2006 Institute of Medicine report that highlighted the crisis of inadequate emergency surgical care in the United States that included care of the mutilated hand.[7],[8] As a result of this study, a partnership was established between ASSH and the American College of Surgeons which has led to changes in Level I centre guidelines mandating 24/7/365 care of the mutilated hand and other microvascular emergencies. Based on our work a regional hand trauma care system has been established that will be capable of providing microvascular surgery at designated hand trauma centres throughout the United States.
Figure 1: (a and b) A 7-year-old patient had incomplete amputation of the arm at the level of mid-humerus. (c-f) Underwent microvascular repair using a shunt and then reversed saphenous vein graft, fasciotomy, neural repair of median and radial nerve and osteosynthesis for humeral fixation as well as skin grafting. (g) Underwent endoscopic tissue expansion for aesthetic recontouring and treatment of keloid. (h and i) Aesthetic and functional result at 1 year

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As more experience was gained in digital replantation, major limb replantation and salvage of mutilating injuries, the concepts of microsurgery were broadened to include autologous tissue transplantation.[9],[10],[11],[12] The development of ‘free tissue transfer’ was introduced by Daniel and Taylor in 1973 when the first groin flap was reported, ushering in a new era of reconstructive surgery. Reconstructive microsurgery began with revascularisation and microneural repair, which led to our ability to perform autologous tissue transfer and has now expanded further with the application of vascularised composite tissue allotransplantation.[13]

Throughout surgical history, efforts to treat a variety of disorders of the upper and lower extremity have been essentially reconstructive, substituting autologous tissues (as a pedicle or free flap) or non-vascularised allografts (bone, tendon nerve) tissue to repair extremities impaired by trauma, tumour, sepsis or congenital differences. Currently, restorative surgery is possible using vascularised composite allotransplantation (VCA) to completely restore all missing structures. Hand, arm and lower limb vascularised composite tissue allotransplantation have been performed with varying degrees of function reestablished in select patients.[14]


  The Development of Orthoplastic Surgery Top


The evolution of surgical specialties began at the conclusion of the 19th century. The origins of reconstructive plastic surgery were based on care for the war injured during World War I. Considered the father of reconstructive plastic surgery, Sir Harold Gillies’ principles to ‘replace like in kind’, were based on treatment of soldiers injured during trench warfare. Modern advances in surgery such as implant arthroplasty, rigid osteosynthesis, aesthetic surgery and microsurgery have resulted in surgical disciplines developing their own specialty societies such as the ASSH, Orthopaedic Trauma Association, American Society for Reconstructive Microsurgery, and the American Society of Plastic Surgery.

Probably, the first modern orthopaedic/plastic surgery collaboration occurred between orthopaedic surgeon W. Arbuthnot Lane and plastic surgeon Sir Harold Gillies. In 1919, Lane wrote the preface for Gillies’ first textbook on plastic surgery. The trauma experience of surgeons in World War I, World War II (Sterling Bunnell), Vietnam (George Omer) and more recently in Afghanistan and Iraq (Dana Covey, Scott Tintle, Kyle Potter) has led to a number of advancements in orthopaedic and plastic surgery.[15] Orthopaedics is a discipline that is by definition predominately dedicated to musculoskeletal function and biomechanics. Plastic surgery is a discipline that is dedicated to soft-tissue reconstruction and aesthetics. We first defined the integration of these two specialties and refer to this field as ‘orthoplastic surgery’ and defined it as: A treatment approach that requires the principles and practices of both specialties of orthopaedic surgery and plastic surgery to be applied to clinical problems simultaneously.[16]

In the later part of the last millennium, government agencies, surgical societies, hospitals and insurance companies began to suggest that surgeons provide ‘outcome data’ relating to cost and patient satisfaction to determine whether complex microsurgical procedures actually help patients and improve quality of life. As a result, we established a method to create a microsurgery database and defined the costs for reconstructive microsurgical procedures in order to provide real dollar value to health systems, patients and insurance agencies.[17],[18] The orthoplastic approach has enabled hospitals to decrease costs and increase patient satisfaction due to efficiency of care, which is essential in today's healthcare climate.

Orthoplastic extremity reconstructive surgery may be categorised into the treatment of traumatic, oncologic and septic conditions. In addition to understanding the indication for amputations and the alternatives to limb salvage such as prosthetics, we have developed a unique approach for treatment of the amputee that optimises residual limb length and function using microsurgical techniques.[19] These include the use of island pedicle or free flaps or emergency fillet flaps to preserve not only sensibility but also to provide coverage. The concept of fillet flaps with their classification, indications and analysis of their clinical value has been described in a multinational report[20],[21] [Figure 2].
Figure 2: (a) 3C Injury in 8-year-old female – not a candidate for salvage. (b) Emergency free fillet of leg and foot for salvage of below knee amputation level. (c) Post-operative result at 2 years with reinnervation of flap and residual limb. (d) Leg in prosthesis

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  Timing of Tissue Transfer and Monitoring Top


Following the important contributions of the late Marko Godina that included the concepts of emergency free tissue transfer, heterotopic replantation and end to side anastomosis for free tissue transfer, we expanded definitions of the emergency free flap, early coverage, primary and secondary microvascular reconstruction in an attempt to support the concept of early coverage whenever possible and staged extremity reconstruction when clinical and patient factors dictate such an approach.[22] It has served to help answer the question of the optimal timing of wound coverage and indications for immediate complete reconstruction as advocated by Godina (relying heavily on emergency free tissue transfer) compared with staged reconstruction using microsurgical techniques. There is a place for both approaches.[23]

In addition to defining new principles for extremity reconstruction using microsurgical techniques, we have investigated a variety of methods for monitoring flap viability and tissue perfusion. While we believe the time honoured method is always serial clinical observation by the surgeon and trained allied health personnel, we reported our experience with the laser Doppler.[24] It was effective at identifying acute arterial and venous thrombosis, but flap monitoring has evolved from the use of the laser Doppler that measured blood flow only in the superficial capillary bed, to the use of implantable Doppler probes which is currently our method of choice of invasive monitoring. These probes provide audible signals of pulsatile flow for arteries and venous flow that confirm vascular patency. We published one of the early clinical reports on the use of indocyanine green with the SPY system (Novadaq/Stryker) in an attempt to decrease free-flap partial necrosis.[25] This technology is similar to the use of fluorescein and a Woods lamp that historically was used to assess tissue perfusion.

Our experience with pharmacologic agents for preventing thrombosis in microvascular surgery has been recently subjected to an evidence-based review and despite the use of heparin and other rheological agents, there is little evidence in the literature to support the use of heparin routinely for free tissue transfer.[26]


  Contributions to Tissue Tranfer Procedures Top


The evolution of intrinsic flaps and flap choices based on angiosomes and perforator vessels has added an armamentarium of soft-tissue reconstructive techniques for surgery of the upper and lower extremities.[27] While these flaps are considered non-microsurgical procedures because microvascular anastomosis is not required, the techniques of harvest are identical to those used in free tissue transfer. These have been popularised in North America and are now considered standard procedures for soft-tissue reconstruction. Similarly, the use of perforator-based pedicle flaps in the foot and ankle and leg has resulted in selection of these methods for coverage as an alternative to free tissue transfer. Although the use of lower extremity pedicle flaps has appeal, complication rates such as partial flap loss have been higher than patients that have undergone free tissue transfer for similar defects. According to our report on 70 sural flaps, this is particularly true in the dysvascular and diabetic limb.[28]

The uses of muscle and musculocutaneous flaps have been effective in the early era of microsurgery and have been effective in the treatment of musculoskeletal infections. An example of this is the use of the pedicle latissimus flap that can be used for elbow coverage and functional restoration of biceps and triceps function following trauma, infection or tumour resection of arm compartments. The use of muscle flaps in septic cases has been the subject of our investigative work in the laboratory and clinically.[29],[30],[31],[32]

As microsurgical techniques extended to peripheral nerve repair and reconstruction, applications of innervated functional muscle transfers for motor restoration have taken their place in the armamentarium of free tissue transfer techniques. The author first observed these techniques in 1977 while visiting the late Kenya Tsuge (Chairman of Orthopaedic Surgery, Hiroshima University School of Medicine), who first described this technique with colleague Yoshikazu Ikuta in 1976. We recently summarised the state of the art of this powerful technique of functional muscle transfer using the gracilis muscle for biceps and forearm flexor reconstruction.[33]


  Advances in Extremity Vascular Reconstruction Top


Microsurgical techniques have proven to be particularly effective for a variety of conditions that result in vascular insufficiency of the upper and lower limb. Our experience with acute upper and lower extremity revascularisation resulting from trauma, digital artery bypass for digital ischaemia, arterial sympathectomy and our use of thoracoscopic sympathectomy has relieved pain and salvaged digits in patients affected by lupus, scleroderma and Buerger's disease.[34] It is even possible to revascularise the hand by arterialisation of the venous system if distal arterial targets are not available for bypass. Borrowing from the vast experience of vascular surgery, our reported use of arteriovenous loops and liberal use of interposition grafts in elective microvascular surgery facilitated improved outcomes of free tissue transfer in extremities that had inadequate recipient vessels in the area of flap placement.[35] Vein grafts for both arterial and venous interposition have been used as long as 37 cm with resultant free-flap survival.

Our experimental work on the use of magnets for vessel anastomosis as an alternative for suture coaptation of blood vessels has been applied in an animal model but has not been adapted clinically.[36]


  The Development of Endoscopic Techniques for Extremity Reconstruction Top


In 1995, we identified a ‘fascial cleft’ in the upper and lower limb based on anatomic research.[37] The fascial cleft is a constant potential anatomic space that can be expanded with balloon dissectors, resulting in the creation of an optical cavity. These dissectors were originally developed for use in endoscopic surgery such as in repair of inguinal hernias. This work in our cadaver laboratory resulted in the development of a series of techniques that were designed to create a ‘minimally invasive approach to extremity reconstruction and microsurgery.’[38] Using the balloon dissector and endoscopic instruments several techniques were developed that included endoscopic harvest of the latissimus dorsi muscle, gracilis muscle, sural nerve and were compared to the morbidity of open harvest of these flaps.[39],[40],[41]

Endoscopic plating techniques were also developed for the humerus and pelvis using this technology that included endoscopic visualisation of the radial nerve and facilitation of endoscopic pelvic osteosynthesis.[42],[43],[44]

Following our work on endoscopic flap harvest, the concept of endoscopic fasciotomy was developed for treatment of exertional compartment syndrome of the upper and lower extremity as well as endoscopic tissue expansion and free-flap pre-expansion, resulting in improved patient outcomes with less patient morbidity[45] [Figure 3]. These techniques also resulted in improved methods for aesthetic reconstruction of the traumatised extremity. This concept of aesthetic restoration of extremities is particularly important in females following extremity trauma and limb salvage. For example, the ability to eliminate fasciotomy wounds that have been skin grafted by tissue expansion of adjacent normal skin and subsequent resurfacing has helped ease the psychological burden of a scarred extremity.
Figure 3: (a) Crush injury to thigh in 7-year-old. No active extension of knee due to scarring. (b) Latissimus flap design. (c) Endoscopic balloon dissector used to create expander pocket. (d) Tissue expander to pre-expand latissimus. (e) Final results – expander capsule used to create new vascularised quadriceps tendon for extension. Primary donor site closure and aesthetic recontouring of thigh

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  Advancements in Vascularised Bone Grafting Top


One of the most versatile microsurgical techniques is the use of vascularised bone tissue, specifically the fibula. The vascularised fibula has undergone an evolution of design, beginning with autogenous transplantation of vascularised bone only. Beginning with the first reports on the use of the fibula for extremity reconstruction in the 1970's, the popularity of the peroneal artery system that can be used to supply skin, muscle and even innervated tissue has increased.[46] An example of this type of reconstruction is the osteocutaneous fibula graft for treatment of complex forearm injuries.[47] Our experience with the osteocutaneous fibula transfer has been reported for trauma, tumour and infection in the upper extremity.[48],[49],[50] The application of the osteocutaneous fibula for clavicular non-union, shoulder arthrodesis, humerus intercalary reconstruction, elbow arthrodesis, forearm axis reconstruction and intercalary reconstruction, wrist arthrodesis and even metacarpal reconstruction represents the versatility of this flap and its utilisation in problems that have arisen from failed conventional grafting, infection, radiation and tumour resection.[51] The vascularised fibula has been used in reconstruction of the pelvic ring, in the lower extremity for femoral and tibial intercalary reconstruction, knee arthrodesis, ankle arthrodesis and avascular necrosis of the femoral head. We have reported on the use of the vascularised fibula as a pedicle flap for knee arthrodesis and ankle arthrodesis in select cases. A special use of the vascularised fibular graft is the application of the vascularised epiphyseal transfer for bony reconstruction in children.[52] The ability to transfer a growing physis has revolutionised paediatric tumour reconstruction and our experience has been recently reported, demonstrating growth in the humerus in all patients. Donor morbidity in cases of epiphyseal transfer includes transient peroneal nerve palsy due to the division of branches of the motor nerve during harvest. These nerves are repaired after the fibula is removed. All patients in this series had recovery of foot eversion [Figure 4].
Figure 4: (a and b) 5-year-old child with Ewing's Sarcoma of humerus (X-ray and magnetic resonance imaging). (c) Resection and staged reconstruction. (d) Early post-operative result. (e) Healing at 1 year – physis open. Stress fracture of fibula healed

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We have reported on the use of the vascularised fibular graft for lumbar spine surgery in cases of infected lumbar fusion.[53] The vascularised fibula can be used as an intercalary strut to stabilise the anterior column of the spine in cases of failed anterior reconstruction due to loosening of hardware and infection. The fibula is vascularised by either direct anastomoses to lumbar perforating vessels or coaptation to the aorta (end to side). The gonadal vein is effective for venous outflow. The aortic anastomosis is performed with assistance from vascular surgeons.

Recently, we have adapted the osteocutaneous medial geniculate artery flap as another option for combined defects of the bone and soft tissue[54] [Figure 5]. This composite flap has been utilised in small bone defects of the humerus, forearm, carpus (scaphoid and lunate) metacarpal and foot. Donor morbidity is minimal and this flap is widely applicable to other areas requiring vascularised bone transfer. The versatility of the medial geniculate artery system includes the use of vascularised periosteum than can be used as a living onlay bone graft to promote healing in cases of non-union. A flap can be designed and harvested such that it is flexible enough to wrap around a non-union site to promote bone healing.
Figure 5: (a and b) Non-union of ankle arthrodesis. (c) Medial geniculate artery free-flap design. (d) Deformity correction-bone gap with deficiency of soft tissue. (e) Post-operative with healed skin flap and bone graft using medial geniculate artery osteocutaneous flap

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  Flap Modifications Top


Our studies over the last 25 years have reported on the evolution and applications of microsurgical tissue transfer. Based on anatomic research, we have developed new tissue transfers and clinical applications of perforator flaps. These advances are based on the vascular territories of the thoracodorsal artery, peroneal artery, lateral femoral circumflex artery, medial geniculate artery and radial artery.[55],[56] All of these flap modifications have been designed to decrease donor site morbidity and expand the armamentarium of autologous vascularised tissue transplantation based on our anatomic and experimental work. Investigations into flap failure and methods to prevent vasospasm have improved flap survival rates experimentally and clinically.[57]

The orthoplastic concept of aesthetic limb reconstruction has far reaching implications for the patient, making the extremity look better as well as function better and has potential psychological benefits to our patients that are reminded of the stigmata of trauma as they see their scars and bulky flaps. Use of lasers, debulking and scar revision are now considered the final reconstructive procedures to optimise limb appearance.[58]


  Foot and Ankle Reconstruction Top


Orthoplastic concepts and microvascular techniques have been particularly helpful in the care of the foot and ankle. Early work applying soft-tissue reconstruction principles to problems associated with calcaneal open reduction and internal fixation resulted in a classification system that clearly provides guidelines for various soft-tissue problems associated with osteosynthesis of the calcaneus.[59] Other advances in traumatic care of the foot and ankle have been reported describing the treatment of lawnmower injuries in children.[60] These injuries are completely preventable, and the tragedy of mutilating injuries in children often resulting in amputation has been mitigated by the use of microsurgical techniques and orthoplastic principles.

Our extensive experience with foot and ankle microsurgical reconstruction has resulted in the realisation that we often fall short in terms of our reconstructive goals. While we can reliably provide coverage of foot and ankle soft-tissue defects, revision of free tissue transfer to the foot and ankle is the rule rather than the exception, and as a result, we have described the aesthetic units of the foot, which serve as a guideline for selection of free tissue transfer, based on anatomic location (heel cord, plantar surface, dorsum, etc.).[61]

The application of microsurgical techniques has been particularly rewarding in the care of the dysvascular and diabetic foot. Our experience has demonstrated the functional limb salvage of patients who are considered for below knee amputation. Rather than amputation, using a combination of macrovascular and microvascular techniques, we have reported on innovations in limb salvage in this challenging patient population[62] [Figure 6]. This includes the use of conventional bypass grafting to the lower extremity and simultaneous free tissue transfer. In order to assure long-term success of these reconstructions, careful control of blood sugar and adjunctive orthotic care is required.
Figure 6: (a) A 70-year old male with calcaneal osteomyelitis and chronic ulcer. (b) Radial forearm flap design. (c) Result following flap and bypass for inflow

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In addition to soft-tissue reconstruction, we have described the combined use of the Ilizarov technique and microsurgical techniques for salvage of extremities.[63] A classification system was developed to guide treatment of patients requiring coverage and stabilisation following trauma (Type I), deformity correction after flap coverage (Type II), intercalary reconstruction following flap coverage (Type III) and vascularised fibula stabilisation using the Ilizarov method (Type IV) [Figure 7].
Figure 7: (a) Resection tibia and anterior compartment osteosarcoma in 28-year old male. (b) Latissimus free flap and fibula (simultaneous flaps). (c) Ilizarov frame to stabilise fibula. (d) Immediately post-operative. (e) Healing at 1 year. (f) Patient ambulating with brace

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  Vascularised Composite Allotransplantation-The Future Top


In 1998, the first-hand transplantation was performed on a New Zealand prisoner. Despite poor patient selection and ultimate clinical failure resulting in reamputation, this event ushered in a new era of microsurgical extremity reconstruction.[64] Restorative surgery is now possible, representing the highest ‘rung’ on the microsurgical reconstructive ladder [Figure 8]. Our efforts in VCA have allowed us to contribute to this field clinically, educationally and experimentally. Our descriptions on the technical aspects of hand transplant have been published, highlighting unique surgical aspects of this field.[65] Our descriptions of the unique aspects of quadrimembral amputees report the special needs of this severely disabled patient population and rationale for VCA.[64] Our VCA educational workshops have attracted surgeons from around the world to perform cadaveric rehearsals for proximal and distal level amputees, resulting in procedure manuals that optimise transplant efficiency and decrease the risk of technical failure. In addition, our studies have investigated the use of novel immunosuppressive agents such as triptolide, that is, effective in decreasing rejection in a rodent hind limb model if used in combination with cyclosporine.[66] Our experimental work in the research laboratory has resulted in models studying the effect of ischaemia time on acute rejection of allotransplants and immune complexes that effect survival.[67],[68] We have reported on the effect of sequential non-synchronous transplants in the same recipient[69] [Figure 9]. This research model reproduces the clinical scenario that often occurs in long-standing solid organ transplant patients susceptible to extensive cutaneous malignancies requiring extremity reconstruction or limb amputation. We reported using a rodent model, that a primary organ transplant (heart transplant) can continue to function despite a second allogeneic challenge (myocutaneous flap) being transplanted as a second transplantation several weeks after the first transplant. As a result of this experimental work, we performed the world's first paediatric bilateral hand transplant (July 2015).[70] At 1 year following the transplant the patient (quadrimembral amputee) has intrinsic and extrinsic hand function, 10 mm 2-point discrimination and can eat, toilet, clothe himself and write [Figure 10]. We have also described in a case report the functional outcomes at 18 months with additional improvement in adapted abilities of this child.[71]
Figure 8: (a) Quadrimembral amputee. (b) Function of transplanted hands with motor recovery at 1 year. (c) Patient driving

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Figure 9: (a) Schematic of double transplant model. (b) Laboratory set-up

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Figure 10: (a) Paediatric quadrimembral amputee. (b) Intrinsic and extrinsic function of transplanted hands at 1 year

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Further animal studies have resulted in creation of an innervated vascularised elbow transplantation model that holds promise for young patients afflicted by elbow trauma or tumour. In this model, we have demonstrated maintenance of bone vascularity and articular cartilage viability[72] [Figure 11].
Figure 11: (a-d) Rodent anatomic dissection vascularised elbow joint

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In regards to our efforts to provide education in this new field, we have described the basic principles of transplant immunology for the hand surgeon, which is essential for members of the hand surgery community interested in upper extremity VCA.[73] In addition to our clinical and experimental work, we have published an overview of hand transplantation outlining the ethical, clinical, immunologic, regulatory and economic challenges of this new field.[74],[75],[76]

The last 57 years mark a remarkable period in the history of extremity surgery. The foundation for the spectrum of concepts and advances presented here are based on four decades of research in reconstructive surgery and extremity reconstruction. Our contributions in replantation, free tissue transfer, vascularised bone grafting, orthoplastic approaches for extremity reconstruction and hand transplantation in adults and children have significantly improved limb reconstruction and salvage. This orthoplastic evolution will continue and we are optimistic about the continued application of microsurgical techniques for care of the upper and lower extremity. Fostering science and research directed towards solving the immunologic barriers in allotransplantation and advancing this evolving field will hold great promise for the future of orthoplastic extremity reconstruction.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gelberman RH, Urbaniak JR, Bright DS, Levin LS. Digital sensibility following replantation. J Hand Surg Am 1978;3:313-9.  Back to cited text no. 1
    
2.
O'Farrell DA, Montella BJ, Bahor JL, Levin LS. Long-term follow-up of 50 duke silicone prosthetic fingers. J Hand Surg Br 1996;21:696-700.  Back to cited text no. 2
    
3.
Zenn MR, Levin LS. Multiple Digit Replantation. The Mutilated Hand. Philadelphia: Elsevier Mosby; 2005.  Back to cited text no. 3
    
4.
Heitmann C, Levin LS. Alternatives to thumb replantation. Plast Reconstr Surg 2002;110:1492-503.  Back to cited text no. 4
    
5.
Heitmann C, Levin LS. Distraction lengthening of thumb metacarpal. J Hand Surg Br 2004;29:71-5.  Back to cited text no. 5
    
6.
Lawson R, Levin LS. Principles of free tissue transfer in orthopaedic practice. J Am Acad Orthop Surg 2007;15:290-9.  Back to cited text no. 6
    
7.
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 Am 2007;32:541-7.  Back to cited text no. 7
    
8.
Friedrich JB, Poppler LH, Mack CD, Rivara FP, Levin LS, Klein MB. Epidemiology of upper extremity replantation surgery in the united states. J Hand Surg Am 2011;36:1835-40.  Back to cited text no. 8
    
9.
Levin LS. New developments in flap techniques. J Am Acad Orthop Surg 2006;14:S90-3.  Back to cited text no. 9
    
10.
Lerman OZ, Haddock N, Elliott RM, Foroohar A, Levin LS. Microsurgery of the upper extremity. J Hand Surg Am 2011;36:1092-103.  Back to cited text no. 10
    
11.
Levin LS. Reconstructive Ladder. Techniques in Orthopaedics. Vol. 10. Philadelphia: Lippincott-Raven; 1995. p. 88-93.  Back to cited text no. 11
    
12.
Gupta A, Shatford R, Woff T, Tsai TM, Scheker L, Levin LS. Instructional course lectures, The American academy of orthopaedic surgeons – Treatment of the severely injured upper extremity. J Bone Joint Surg 1999;81A:1628.  Back to cited text no. 12
    
13.
Tintle SM, Levin LS. The reconstructive microsurgery ladder in orthopaedics. Injury 2013;44:376-85.  Back to cited text no. 13
    
14.
Tintle SM, Potter BK, Elliott RM, Levin LS. Hand transplantation. JBJS Rev 2014;2. pii: 01874474-201401000-00003.  Back to cited text no. 14
    
15.
Lerman OZ, Kovach SJ, Levin LS. The respective roles of plastic and orthopedic surgery in limb salvage. Plast Reconstr Surg 2011;127 Suppl 1:215S-227S.  Back to cited text no. 15
    
16.
Levin LS. The reconstructive ladder. An orthoplastic approach. Orthop Clin North Am 1993;24:393-409.  Back to cited text no. 16
    
17.
Allen DM, Hey LA, Heinz TR, Golal R, Levin LS. Development and implementation of an extremity free-tissue-transfer database. J Reconstr Microsurg 1997;13:475-85.  Back to cited text no. 17
    
18.
Heinz TR, Cowper PA, Levin LS. Microsurgery costs and outcome. Plast Reconstr Surg 1999;104:89-96.  Back to cited text no. 18
    
19.
Erdmann D, Sundin BM, Yasui K, Wong MS, Levin LS. Microsurgical free flap transfer to amputation sites: Indications and results. Ann Plast Surg 2002;48:167-72.  Back to cited text no. 19
    
20.
Küntscher MV, Erdmann D, Homann HH, Steinau HU, Levin SL, Germann G, et al. The concept of fillet flaps: Classification, indications, and analysis of their clinical value. Plast Reconstr Surg 2001;108:885-96.  Back to cited text no. 20
    
21.
Levin LS, Erdmann D, Germann G. The use of fillet flaps in upper extremity construction. J Am Soc Surg Hand 2000;2:39-44.  Back to cited text no. 21
    
22.
Levin LS, Erdmann D. Primary and secondary microvascular reconstruction of the upper extremity. Hand Clin 2001;17:447-55, ix.  Back to cited text no. 22
    
23.
Levin LS. Early versus delayed closure of open fractures. Injury 2007;38:896-9.  Back to cited text no. 23
    
24.
Heller L, Levin LS, Klitzman B. Laser Doppler flowmeter monitoring of free-tissue transfers: Blood flow in normal and complicated cases. Plast Reconstr Surg 2001;107:1739-45.  Back to cited text no. 24
    
25.
Pestana IA, Coan B, Erdmann D, Marcus J, Levin LS, Zenn MR. Early experience with fluorescent angiography in free-tissue transfer reconstruction. Plast Reconstr Surg 2009;123:1239-44.  Back to cited text no. 25
    
26.
Levin LS, Cooper EO. Clinical use of anticoagulants following replantation surgery. J Hand Surg Am 2008;33:1437-9.  Back to cited text no. 26
    
27.
Germann G, Levin LS. Intrinsic flaps in the hand: New concepts in skin coverage. Tech Hand Up Extrem Surg 1997;1:48-61.  Back to cited text no. 27
    
28.
Baumeister SP, Spierer R, Erdmann D, Sweis R, Levin LS, Germann GK. A realistic complication analysis of 70 sural artery flaps in a multimorbid patient group. Plast Reconstr Surg 2003;112:129-40.  Back to cited text no. 28
    
29.
Brown SA, Mayberry AJ, Mathy JA, Phillips TM, Klitzman B, Levin LS. The effect of muscle flap transposition to the fracture site on TNFalpha levels during fracture healing. Plast Reconstr Surg 2000;105:991-8.  Back to cited text no. 29
    
30.
Heitmann C, Patzakis MJ, Tetsworth KD, Levin LS. Musculoskeletal sepsis: Principles of treatment. Instr Course Lect 2003;52:733-43.  Back to cited text no. 30
    
31.
Heitmann C, Higgins LD, Levin LS. Treatment of deep infections of the shoulder with pedicled myocutaneous flaps. J Shoulder Elbow Surg 2004;13:13-7.  Back to cited text no. 31
    
32.
Zalavras CG, Marcus RE, Levin LS, Patzakis MJ. Management of open fractures and subsequent complications. J Bone Joint Surg Am 2007;89:884-95.  Back to cited text no. 32
    
33.
Fischer JP, Elliott RM, Kozin SH, Levin LS. Free function muscle transfers for upper extremity reconstruction: A review of indications, techniques, and outcomes. J Hand Surg Am 2013;38:2485-90.  Back to cited text no. 33
    
34.
Rizzo M, Balderson SS, Harpole DH, Levin LS. Thoracoscopic sympathectomy in the management of vasomotor disturbances and complex regional pain syndrome of the hand. Orthopedics 2004;27:49-52.  Back to cited text no. 34
    
35.
Ritter EF, Anthony JP, Levin LS, Demas CP, Klitzman B, Skarad D, et al. Microsurgical composite tissue transplantation at difficult recipient sites facilitated by preliminary installation of vein grafts as arteriovenous loops. J Reconstr Microsurg 1996;12:231-40.  Back to cited text no. 35
    
36.
Erdmann D, Sweis R, Heitmann C, Yasui K, Olbrich KC, Levin LS, et al. Side-to-side sutureless vascular anastomosis with magnets. J Vasc Surg 2004;40:505-11.  Back to cited text no. 36
    
37.
Levin LS, Rehnke R, Eubanks S. Endoscopic surgery of the upper extremity. Hand Clin 1995;11:59-70.  Back to cited text no. 37
    
38.
Ip TY, Aponte R, Koger KE, German G, Zobrist R, Levin LS. Use of the balloon dissector in minimally invasive aesthetic and reconstructive surgery. Ann Plast Surg 1998;40:205-13.  Back to cited text no. 38
    
39.
Lin CH, Wei FC, Levin LS, Chen MC. Donor-site morbidity comparison between endoscopically assisted and traditional harvest of free latissimus dorsi muscle flap. Plast Reconstr Surg 1999;104:1070-7.  Back to cited text no. 39
    
40.
Lin CH, Levin LS. Free flap expansion using balloon-assisted endoscopic technique. Microsurgery 1996;17:330-6.  Back to cited text no. 40
    
41.
Van Buskirk ER, Rehnke RD, Montgomery RL, Eubanks S, Ferraro FJ, Levin LS. Endoscopic harvest of the latissimus dorsi muscle using the balloon dissection technique. Plast Reconstr Surg 1997;99:899-903.  Back to cited text no. 41
    
42.
Baumeister S, Follmar KE, Erdmann D, Baccarani A, Levin LS. Tissue expansion of free and pedicled flaps after transfer: Possibilities and indications. J Reconstr Microsurg 2007;23:63-8.  Back to cited text no. 42
    
43.
Zobrist R, Messmer P, Levin LS, Regazzoni P. Endoscopically controlled stabilization of humerus shaft fractures. The endoscope as an aid in minimally invasive osteosynthesis. Unfallchirurg 2002;105:246-52.  Back to cited text no. 43
    
44.
Levin LS, Zobrist R, Aponte R. Endoscopic plating of the pelvis. J Orthop Trauma 2002;16:264-71.  Back to cited text no. 44
    
45.
Wittstein J, Moorman CT 3rd, Levin LS. Endoscopic compartment release for chronic exertional compartment syndrome. J Surg Orthop Adv 2008;17:119-21.  Back to cited text no. 45
    
46.
Heitmann C, Khan FN, Levin LS. Vasculature of the peroneal artery: An anatomic study focused on the perforator vessels. J Reconstr Microsurg 2003;19:157-62.  Back to cited text no. 46
    
47.
Jupiter JB, Fernandez DL, Levin LS, Wysocki RW. Reconstruction of posttraumatic disorders of the forearm. Instr Course Lect 2010;59:283-93.  Back to cited text no. 47
    
48.
Jupiter JB, Gerhard HJ, Guerrero J, Nunley JA, Levin LS. Treatment of segmental defects of the radius with use of the vascularized osteoseptocutaneous fibular autogenous graft. J Bone Joint Surg Am 1997;79:542-50.  Back to cited text no. 48
    
49.
Heitmann C, Erdmann D, Levin LS. Treatment of segmental defects of the humerus with an osteoseptocutaneous fibular transplant. J Bone Joint Surg Am 2002;84-A:2216-23.  Back to cited text no. 49
    
50.
Levin LS. Vascularized fibula graft for the traumatically induced long-bone defect. J Am Acad Orthop Surg 2006;14:S175-6.  Back to cited text no. 50
    
51.
Erdmann D, Bergquist GE, Levin LS. Ipsilateral free fibula transfer for reconstruction of a segmental femoral-shaft defect. Br J Plast Surg 2002;55:675-7.  Back to cited text no. 51
    
52.
Erdmann D, Garcia RM, Blueschke G, Brigman BE, Levin LS. Vascularized fibula-based physis transfer for pediatric proximal humerus reconstruction. Plast Reconstr Surg 2013;132:281e-7e.  Back to cited text no. 52
    
53.
Erdmann D, Meade RA, Lins RE, McCann RL, Richardson WJ, Levin LS. Use of the microvascular free fibula transfer as a salvage reconstruction for failed anterior spine surgery due to chronic osteomyelitis. Plast Reconstr Surg 2006;117:2438-45.  Back to cited text no. 53
    
54.
Haddock NT, Alosh H, Easley ME, Levin LS, Wapner KL. Applications of the medial femoral condyle free flap for foot and ankle reconstruction. Foot Ankle Int 2013;34:1395-402.  Back to cited text no. 54
    
55.
Heitmann C, Guerra A, Metzinger SW, Levin LS, Allen RJ. The thoracodorsal artery perforator flap: Anatomic basis and clinical application. Ann Plast Surg 2003;51:23-9.  Back to cited text no. 55
    
56.
Wang HT, Fletcher JW, Erdmann D, Levin LS. Use of the anterolateral thigh free flap for upper-extremity reconstruction. J Hand Surg Am 2005;30:859-64.  Back to cited text no. 56
    
57.
Kiefer J, Hollenbeck S, Woo S, Earle S, Erdmann D, Levin LS. Impact of Systemic Injury on Free Flap Outcomes in Trauma Patients. 2011. Vol. 128. Plastic and Reconstructive Surgery, European PSRC Abstracts Supplement; 2011. p. 616.  Back to cited text no. 57
    
58.
Heinz T, Levin LS. Aesthetic Considerations After Limb Trauma. Techniques in Orthopaedics. Vol. 10. Philadelphia: Lippincott-Raven; 1995. p. 145-50.  Back to cited text no. 58
    
59.
Levin LS, Nunley JA. The management of soft-tissue problems associated with calcaneal fractures. Clin Orthop Relat Res 1993;290:151-6.  Back to cited text no. 59
    
60.
Erdmann D, Lee B, Roberts CD, Levin LS. Management of lawnmower injuries to the lower extremity in children and adolescents. Ann Plast Surg 2000;45:595-600.  Back to cited text no. 60
    
61.
Hollenbeck ST, Woo S, Komatsu I, Erdmann D, Zenn MR, Levin LS. Longitudinal outcomes and application of the subunit principle to 165 foot and ankle free tissue transfers. Plast Reconstr Surg 2010;125:924-34.  Back to cited text no. 61
    
62.
Oishi SN, Levin LS, Pederson WC. Microsurgical management of extremity wounds in diabetics with peripheral vascular disease. Plast Reconstr Surg 1993;92:485-92.  Back to cited text no. 62
    
63.
Hollenbeck ST, Woo S, Ong S, Fitch RD, Erdmann D, Levin LS. The combined use of the ilizarov method and microsurgical techniques for limb salvage. Ann Plast Surg 2009;62:486-91.  Back to cited text no. 63
    
64.
Foroohar A, Elliott RM, Kim TW, Breidenbach W, Shaked A, Levin LS. The history and evolution of hand transplantation. Hand Clin 2011;27:405-9, vii.  Back to cited text no. 64
    
65.
Mendenhall SD, Schumucker RW, De la Garza M, Lutfy J, Levin LS, Neumeister MW. Osteosynthesis in forearm transplantation using a novel ulnar-shortening osteotomy system for simultaneous both bone fixation. Vascularized Compos Allotransplantation 2015;2:53-9.  Back to cited text no. 65
    
66.
Liu F, Xusong L, Shenghui I, Zhang X, Wang S, Kanchwala S, et al. Immunosuppression with a combination of triptolide and cyclosporin A in rat vascularized groin flap allotransplantation. J Plast Reconstr Surg 2013;131:343e-50e.  Back to cited text no. 66
    
67.
Pradka SP, Ong YS, Zhang Y, Davis SJ, Baccarani A, Messmer C, et al. Increased signs of acute rejection with ischemic time in a rat musculocutaneous allotransplant model. Transplant Proc 2009;41:531-6.  Back to cited text no. 67
    
68.
Xu H, Dahiya S, Wang L, Akimova T, Han R, Zhang T, et al. Utility of IL-2 complexes in promoting the survival of murine orthotopic forelimb vascularized composite allografts. Transplantation 2018;102:70-8.  Back to cited text no. 68
    
69.
Yang J, Erdmann D, Chang JC, Komatsu I, Zhang Y, Wang D, et al. A model of sequential heart and composite tissue allotransplant in rats. Plast Reconstr Surg 2010;126:80-6.  Back to cited text no. 69
    
70.
Amaral S, Levin LS. Pediatric and congenital hand transplantation. Curr Opin Organ Transplant 2017;22:477-83.  Back to cited text no. 70
    
71.
Amaral S, Kessler SK, Levy TJ, Gaetz W, McAndrew C, Chang B, et al. 18-month outcomes of heterologous bilateral hand transplantation in a child: A case report. Lancet Child Adolesc Health 2017;1:35-44.  Back to cited text no. 71
    
72.
Tang J, Zhu H, Luo X, Li Q, Levin LS, Tintle SM. A vascularized elbow allotransplantation model in the rat. J Shoulder Elbow Surg 2015;24:779-86.  Back to cited text no. 72
    
73.
Ravindra K, Haeberle M, Levin LS, Ildstad ST. Immunology of vascularized composite allotransplantation: A primer for hand surgeons. J Hand Surg Am 2012;37:842-50.  Back to cited text no. 73
    
74.
Levin LS. The American Society for Surgery of the Hand Council: ASSH position statement on hand transplantation 2013. J Hand Surg 2013;38:2234-5.  Back to cited text no. 74
    
75.
Tintle SM, Potter BK, Elliott RM, Levin LS. Hand transplantation. JBJS Rev 2014;2. pii: 01874474-201401000-00003.  Back to cited text no. 75
    
76.
McDiarmid SV, Levin LS, Luskin RS. Vascularized composite tissue allografts (VCA): The policy side. Curr Transplant Rep 2016;3:50-6.  Back to cited text no. 76
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]



 

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Early History
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