Lower Limb Vascularized Composite Allotransplantation

25 Lower Limb Vascularized Composite Allotransplantation

Pedro C. Cavadas

Summary

Lower limb vascularized composite allotransplantation (VCA) is not immunologically different from solid organ transplantation; so any recipients will require lifelong immune suppression (IS) to prevent rejection, and expect the risks of significant metabolic and renal toxicity, opportunistic infections, and an increased peril of malignancy. As such, lower limb VCA would be justifiable only if the expected improvement of the quality of life of the patient would be enormous. Prior knee joint VCA has been reported with overall negative results. Presented here is the first case of lower limb VCA in a wheelchair-dependent bilateral traumatic above-knee amputee. Active range of motion even of the feet was subsequently possible, but complications at postoperative month 15 required reamputation of both legs. Lower limb VCA therefore remains very controversial and is a subject of continuing debate as for any clear indications. The limiting factor as shown is not the surgical technique, but rather the necessary IS treatment that must first be mastered.

Keywords: vascularized composite allotransplantation, lower limb allotransplantation, immune suppression

25.1 Introduction

Solid organ transplantation (SOT) is now considered a standard of care for various end-stage organ failures. Based on the wealth of knowledge generated by SOT during the past five decades, nonvital organ transplantation (mainly visible segments of the musculoskeletal system) has been introduced relatively recently. These “organs,” the so-called vascularized composite allotransplantations (VCAs), are a markedly heterogeneous group of structures (limbs, abdominal wall, face, uterus, larynx, penis) grouped together because of their composite-tissue nature and/or the need for nerve regeneration to achieve function. VCAs are not immunologically different from SOT; so recipients of VCA require lifelong immune suppression (IS) to prevent rejection, at the expense of significant metabolic and renal toxicity, opportunistic infections (such as cytomegalovirus [CMV] infections), and an increased risk of malignancy. Given these risks, VCAs are indicated only if the expected improvement of the quality of life of the patient is enormous.

The world’s experience in VCA approaches 150 cases, mainly including the upper limb (hand, forearm, and arm), abdominal wall, and facial segments.¹,² The short- and mid-term results obtained in upper limb transplantation have been remarkably good with functional results comparable to same-level replantations.²

Lower limb allotransplantation enthusiasm has not paralleled that of the upper limb. There are several reasonable explanations. Below-knee (BK) amputees are generally able to walk quite well with prostheses. Above-knee (AK) amputees, especially if bilateral, are much more difficult to rehabilitate.³,⁴ Osseointegrated AK prostheses have been described, although the complication rate is high.⁵ Lower limb replantation itself has historically been discouraged, in sharp contrast to upper limb replantation. Results have been stated to be poor, and prostheses traditionally considered the better treatment of choice.⁶,⁷,⁸ Most surgeons are thus not familiar with systematic lower limb replantation. However, encouraging results of leg replantation have been published recently.⁹,¹⁰

Compared to the upper limb, the lower limb performs a much more basic function in most people. For a fundamental gait, hip extensor–abductors (glutei medii muscles), knee extensors (quadriceps), and a plantigrade support are the minimum requisites. Plantar protective sensation is also desirable for long-term plantar integrity. Achieving all these basic functions with a lower limb VCA seemed to be a realistic goal in a bilateral AK amputee, and for this reason, Cavadas et al performed the first lower limb allotransplantation in July 2011.¹¹,¹² There were no precedents in the medical literature, but planning was based on solid clinical grounds.

A case usually cited as the first lower limb allotransplantation was the excellent clinical report by Zuker et al in 2006 in which one leg was transferred between conjoined twins.¹³,¹⁴ Although technically brilliant, this was autologous tissue, without IS therapy, and thus cannot be considered an allotransplantation. Experience with knee joint VCA has been reported by Diefenbeck et al¹⁵ and Hoffmann and Kirschner¹⁶ in a heterogeneous group of patients, some without a skin island monitor to detect acute rejection (AR), with overall negative results. This is in striking contrast with the relatively benign behavior of allogenic joints in upper limb transplants.

25.2 Clinical Example of Lower Limb Vascularized Composite Allotransplantation

The recipient was a 22-year-old man, who was a wheelchair-dependent bilateral traumatic AK amputee. The right side level was mid-shaft femur, and left side was the distal third (▶ Fig. 25.1). CMV immunoglobulin G (IgG) was negative and Epstein–Barr virus (EBV) IgG was positive. The donor was a 26-year-old woman ABO-compatible multiorgan donor. CMV and EBV IgG were negative, and there was total HLA mismatch—and a complete human leukocyte antigen (HLA) mismatch. Transplantation was performed on July 11, 2011, by a single surgeon with three assistants. Relevant structures were dissected and tagged bilaterally in the stumps of the recipient. The external iliac vessels were used as the recipient vascular sites. The procurement of the legs was performed in an adjacent operating room after cardiac and liver retrieval. The infrarenal aorta was not cross-clamped, allowing simultaneous in situ perfusion of the lower extremities with cold UW (University of Wisconsin) solution.

The right leg was transplanted first (▶ Fig. 25.2). The sequence of repairs was the same on both sides. Bone fixation was performed initially with lateral 4.5-mm locking plates without X-ray control for expediency. Hamstring muscles were next repaired en bloc with moderate tension. The knee was extended and the sciatic nerve repaired. The quadriceps muscle was sutured under maximal tension. In order to minimize the hemodynamic and hypothermic insult, the following sequence of limb rewarming, vascular refilling, and clamp management was performed. The iliac artery of the VCA was flushed with warm (35 °C) Ringer’s solution. The vascular bed of the leg was filled with warm Ringer’s solution and the artery and vein clamped. End-to-side anastomoses were performed to the recipient’s external iliac vessels. The vein clamp was released first, and then the arterial clamps, allowing revascularization. The left leg was kept cooled during the right side reattachment, and the same sequence of surgical maneuvers was followed on the left side (▶ Fig. 25.3). Total ischemia time was 3.5 hours on the right side and 5.5 hours on the left side. No fasciotomies were performed. No adverse intraoperative hemodynamic events occurred.