Is Skin the Most Allogenic Tissue in Vascularized Composite Allotransplantation and a Valid Monitor of the Deeper Tissues?

Since the 1960s, skin has been considered to be the most allogenic tissue in humans. This tenet has remained unquestioned in the reconstructive transplant arena, which has led to skin serving as the sole monitor for early rejection in vascularized composite allotransplantation. In this article, the authors question the validity of this belief. The authors' hypothesis is that skin is not always an accurate monitor of rejection in the deep tissues, thus questioning the positive and negative predictive value of the punch biopsy for suspected vascularized composite allotransplantation rejection. A search was carried out identifying vascularized composite allotransplantation publications where the allogenicity of transplanted skin was evaluated. Eighteen publications claimed skin was found to be the most allogenic tissue in humans, justifying its use as a superior monitor for rejection. Eight publications demonstrated skin to be a poor monitor of rejection deeper to the skin. Two vascularized composite allotransplantation animal studies reported skin rejecting simultaneously with the deeper tissues. Finally, three publications discussed a skin and kidney allograft, transplanted simultaneously, indicating skin allogenicity was equivalent to the that of the kidney allograft. Much of the literature in human vascularized composite allotransplantation claims skin to be an excellent monitor of the deep tissues. The conclusion from this study is that skin does not always function as a good monitor for what could be rejecting in the deep tissues. The authors believe continued research is necessary to focus on expanding novel monitoring techniques and technologies to accurately diagnose vascularized composite allotransplantation rejection without tissue destruction.

Composite and Multivisceral Transplantation: Nomenclature, Surgical Techniques, Current Practice, and Long-term Outcome.

The successful development of multivisceral and composite visceral transplantation is among the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathologic conditions. The outcome has markedly improved over the last 3 decades owing to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.

Effect of the vascularized bone components on the survival of vascularized composite allografts.

BACKGROUND: Vascularized composite allograft (VCA), such as hand and face allograft, contains a vascularized bone component that may provide an immunologic benefit and induce tolerance for the simultaneous inclusion of marrow cells and a marrow microenvironment. We developed a chimeric groin cutaneous/femur flap to investigate the effect of vascularized bone marrow on VCA survival and its ability to induce chimerism. METHODS: Brown Norway and Lewis rats were used as donors and recipients, respectively. The experimental groups were as follows: groin flap transplantation alone, flap plus intravenous donor bone marrow cells and flap plus simultaneous femur transplantation. Animals received a nonmyeloablative conditioning regimen that consisted of 7-Gy thymic irradiation, 0.75-mL antilymphocyte serum, and 8-mg-1kg-1d cyclosporine A. The flap survival time, peripheral blood chimerism, and the bone marrow of transplanted femurs were analyzed and compared between groups. RESULTS: Our data showed that the conditioning regimen was effective in T cell ablation. Simultaneous femur transplantation significantly prolonged the median flap survival time (78.8 ± 13.0 d, n = 8) compared with the intravenous bone marrow infusion group (60.9 ± 2.2 d, n = 7) and the control group (58.6 ± 1.3 d, n = 5). Peripheral blood chimerism of 5.81% ± 1.98% was persistently detected for 60 d in recipients of femur transplants but not in the other two groups. Viable bone marrow was confirmed within the transplanted femur on postoperative d 60, but it was gradually replaced by recipient origin cells and eventually developed rejection and fibrosis. CONCLUSIONS: Vascularized bone component plays some protective roles on VCA survival but fails to provide a continuous source of donor cells.

Outcomes after hand and upper extremity transplantation.

Hand and upper extremity transplantation (HUET) has emerged as the most frequently performed reconstructive procedure in the burgeoning field of vascularized composite allotransplantation (VCA). VCA refers to a form of transplant with multiple tissue types that represents a viable treatment option for devastating injuries where conventional reconstruction would be unable to restore form and function. As hand transplantation becomes increasingly more common, discussions on advantages and disadvantages of the procedure seem to intensify. Despite encouraging functional outcomes, current immunosuppressive regimens with their deleterious side-effect profile remain a major concern for a life-changing but not life-saving type of transplant. In addition, a growing number of recipients with progressively longer follow-up prompt the need to investigate potential long-term sequelae, such as chronic rejection. This review will discuss the current state of HUET, summarizing outcome data on graft survival, motor and sensory function, as well as immunosuppressive treatment. The implications of these findings for VCA in terms of achievements and challenges ahead will then be discussed.

Facial and hand allotransplantation.

Vascularized composite allotransplantation (VCA) is a novel therapeutic option for treatment of patients suffering from limb loss or severe facial disfigurement. To date, 72 hand and 19 facial transplantations have been performed worldwide. VCA in hand and facial transplantation is a complex procedure requiring a multidisciplinary team approach and extensive surgical planning. Despite good functional outcome, courses after hand and facial transplantation have been complicated by skin rejection. Long-term immunosuppression remains a necessity in VCA for allograft survival. To widen the scope of these quality-of-life-improving procedures, minimization of immunosuppression to limit risks and side effects is needed.

The biophysical characteristics of human composite flexor tendon allograft for upper extremity reconstruction.

INTRODUCTION: Devastating volar hand injuries with significant damage to the skin and soft tissues, pulley structures and fibro-osseous sheath, flexor tendons, and volar plates pose a major problem to the reconstructive hand surgeon. Despite advances in tendon handling, operative technique, and postoperative hand rehabilitation, patients who have undergone flexor tendon reconstruction are often plagued by chronic pain, stiffness, and decreased range of motion with resultant decreased ability to work and poor quality of life. In this article, we expand the technique of human composite flexor tendon allografts (CFTAs), pioneered by Dr E.E. Peacock, Jr, which consist of both the intrasynovial and extrasynovial flexor digitorum superficialis and flexor digitorum profundus tendons and their respective fibro-osseous sheath consisting of the digital pulley structures, periosteum, and volar plates procured from cadaveric donors with the use of modern tissue processing techniques. METHODS: Human cadaveric CFTAs were procured and divided into 2 groups-unprocessed CFTAs and processed CFTAs, which are cleansed and sterilized to a sterility assurance level of 10(-6). Physical length and width relationships as well as tensile strength and gliding resistance assessments were recorded pre-tissue and post-tissue processing. The histologic properties of the composite allografts were assessed before and after tissue processing. RESULTS: There was no significant difference with respect to physical properties of the composite allografts before or after tissue processing. The processed composite allografts demonstrated equivalent maximum load to failure and elastic modulus compared to unprocessed tendons. The gliding resistance of the composite tendon allografts was not significantly different between the 2 groups. CONCLUSIONS: The use of CFTAs addresses the issues of adhesion formation and lack of suitable donor material by providing a source of intrasynovial tendon in its unaltered fibro-osseous sheath without donor morbidity. This approach represents an important step toward designing an ideal material for complex flexor tendon reconstruction, which takes advantage of an intrasynovial flexor tendon in its native fibro-osseous sheath without the need for additional donor morbidity using a construct which can be engineered to have minimal tissue reactivity, negligible potential for disease transmission, and improved tendon healing properties versus standard tendon allograft.