The evolution and success of intestinal and multi-visceral transplantation over the past 20 years have raised the issue of difficult or even impossible abdominal closure, a topic rarely encountered in other fields of transplantation. Different techniques have been proposed to address this topic. The choice depends on the transplant team’s expertise and/or the availability of a plastic surgery service. Abdominal wall transplant is a type of composite tissue allograft that can be utilized to reconstitute the abdominal domains of patients who undergo intestinal transplant, and the results are encouraging. It is an effective option to achieve primary abdominal closure after intestinal transplant. In its full-thickness form, it may be useful for monitoring rejection or viability of visceral organs. Our aim is to review the role of abdominal wall transplant in achieving tension-free closure of the abdomen.
Key words : Abdominal closure, Intestinal transplantation, Vascularized composite allografts
Abdominal catastrophes that necessitate intestinal or multivisceral transplant may also present challenges to major abdominal wall reconstruction. Some of these defects defy conventional reconstructive techniques. Patients who undergo both intestinal and multivisceral transplantation may encounter abdominal wall closure problems. The lack of small and large intestines because of multiple prior surgical procedures and the need to build ostomies can lead to both the reduction of the abdominal domain and extensive scarring of the abdominal wall.1 For patients who have previously undergone complete resection of the midgut, many have lost the abdominal compartment domain. The result can be an abdominal cavity that is often too small to receive transplanted organs. At the end of the organ transplant procedure, organs are often edematous, and a tight closure after liver or intestinal transplant can be detrimental, with increased risks of morbidity and mortality.2
Aims and Methods
To date, there are few publications on the use of abdominal wall transplant (AWT) as a means for large abdominal wall composite defect reconstruction. Since Levi and associates first introduced AWT, there have been 35 cases of abdominal wall allotransplants worldwide, with 88% having flap survival (Table 1).3-5 Although vascularized AWT has been used in a limited number of centers, over time it has affected transplant surgery and may now be adapted for use in other fields.
Here, we aimed to review the evolution and present state and future perspectives of AWT to achieve a successful abdominal wall closure after intestinal transplant. We conducted a literature review using PubMed, Scopus, Google Scholar, MEDLINE, and EMBASE databases, with the following headings: abdominal wall, abdominal wall transplantation, abdominal wall reconstruction, bowel transplantation, intestinal transplantation, small bowel transplantation, mutivisceral transplantation, vascularized composite allotransplantation, and immunosuppression. After title-abstract shifting, 35 articles were retained. Ten articles were excluded, resulting in 25 articles that were the most informative and relevant for this review.
Indications for Abdominal Wall Transplant
Most patients with intestinal transplant have already had many intra-abdominal surgeries before trans-plant. In the literature, various options to overcome the risks faced by these patients have been reported. As described by Moon,6 options to completely close the abdominal wound include (1) use of the patient’s abdominal wall in which a “component’s separation” technique is used to increase the mobility of the flap; (2) staged expansion of the abdominal wall by using a tension-generating/distraction device, a technique used in pediatric patients; (3) use of an artificial mesh, a technique used when the abdominal wall defect is large; (4) use of the peritoneum from a brain-dead donor, which can be used to reinforce the abdominal wall defect; and (5) transplant of the entire abdominal wall from a brain-dead donor. These various abdominal wall reconstruction techniques are summarized in Table 2.6
A simple tension-free and primary abdominal wall closure is not always possible, as many patients have the concomitant existence of a frozen abdomen secondary to multiple abdominal procedures, loss of bowel length from prior bowel resection, presence of multiple fistulas or ostomies, extensive skin lesions secondary to the scarring process of a healed fistula, or a removed ostomy. These findings are most commonly a consequence of processes that lead to short gut syndrome, the primary cause of chronic intestinal failure.7 Two main strategies have been proposed to overcome the need for an adequate closure at the end of the transplant. One strategy is to use a smaller donor or to reduce the length/size of the transplanted graft. The other strategy is to enlarge the abdominal domain. The latter has become the preferred approach. However, AWT may be appropriate for some patients. The risks of lifelong immunosuppression versus the potential clinical benefits of tissue transplant must be considered.8
An obvious reason for the lack of significant prior experiences with abdominal wall-vascularized composite allotransplant (VCA) is the need for immunosuppression for an elective non-lifesaving procedure, with the surgeon thus perhaps not offering this as a viable option to patients. These challenges have arisen before in other domains of VCA, such as hand/upper extremity and facial transplants. In these other domains, improvements in function and quality of life have justified the risks of immunosuppression. However, the indications can be expected to broaden with the push for immunomodulation and decrease in immuno-suppression.4
An exit strategy for abdominal wall VCA failure must also be considered. Presently, emerging biologic materials are being used to reconstitute the fascial layers of the abdominal wall. However, these materials require vascularized tissue support for ingrowth and incorporation. Moreover, long-term outcomes regarding repair durability with these materials have yet to be determined. In most cases, if all other options have failed, skin grafting directly onto the bowel may be performed as a bailout for abdominal wall VCA failure.9
The abdominal wall is recovered from brain-dead donors with a still functioning heart. Recovery involves bisubcostal incisions that are continued along the lateral rectus edges and completed by suprapubic connection (Figure 1). The procedure begins by lifting up an abdominal flap consisting of the median oval cutaneous pan, the underlying bilateral rectus abdominis muscles, and a small part of the oblique muscles and the deep muscular sheet, together with the thin parietal layer of the peritoneum. The external iliac vessels are identified, and the deep inferior epigastric vessels are isolated up to their origin.10
The abdominal flap is then turned over to face downward, which allows retrieval of other abdominal organs. During this phase, the flap is packed with cold water and ice and the other organs are flushed with preservation solution and removed. When the other organs have been retrieved, the epigastric vessels of the flap are sectioned at their origin from the iliac vessels. After flap removal, further cold perfusion is conducted via cannulation of 2 epigastric arteries. The abdominal graft is then stored in a conservation container with ice.11,12 The donor epigastric pedicles are anastomosed end-to-end with the recipient epigastric vessels or circumflex deep inferior vessels. The arterial and venous anastomoses are both fashioned with a 9/0 Prolene suture using a microscope. The abdominal flap is then revas-cularized, with skin color and bleeding from the flap margins indicating adequate perfusion. The surgical procedure is completed with ileostomy formation, suturing of the deep and superficial muscular fascia, and cutaneous suturing.13 During the postoperative period, the function of the small-bowel graft is monitored for acute cellular rejection by repeated biopsies of the intestinal mucosa through the ileostomy. The function of the abdominal wall graft is monitored by biopsies from skin of the flap during the first 2 weeks and subsequently by examination of the color of the skin.14
An additional consideration is the potential advantage of creating a functional abdominal wall over a static reconstruction. This principle has been shown in abdominal wall reconstruction using innervated free flaps. To achieve this, intercostal neurorrhaphy would need to be performed to some degree. It remains to be determined whether 1, 2, 3, or more intercostal nerves are needed to establish functional recovery of an AWT.15
Patients who receive both a VCA and solid organs from one or multiple donors will require a combination of immunotherapy and rejection monitoring, which can complicate postoperative treatment. Furthermore, rejection of the VCA graft presumably may not correlate with rejection of the visceral organs. Status of one graft should be used to assess the status of other grafts despite a single donor. Visceral organ function is arguably more important than that of the VCA for the overall well-being and survival of the patient. This consideration of graft hierarchy highlights the importance of immunosuppressive regimens for both tissue entities and of independent monitoring and management of rejection and immune suppression, even if initially transplanted as a single unit.16
Conventional immunosuppressive strategies that are currently applied to patients who undergo VCA procedures have largely been extrapolated from regimens used in solid-organ transplant. The level of immunosuppressive medication required to ensure graft survival is comparable or even slightly higher than it is for kidney transplant. For instance, according to the International Registry for Hand and Composite Tissue Transplantation, most VCA patients receive either polyclonal (antithymocyte globulins) or monoclonal antibodies (alemtuzumab or basiliximab) as an induction agent, followed by high-dose triple-drug combination therapies, including tacrolimus, mycophenolic acid, and steroids as maintenance therapy.17
Some patients have been switched from tacrolimus to the mammalian target of rapamycin inhibitor sirolimus with the rationale of minimizing renal adverse effects, improving glycemic control, and potentially avoiding chronic vascular changes (myointimal hyperproliferation) and neurotoxicity. It is also important to note that induction therapy involves the more frequent use of anti-CD52.18
Abdominal wall transplant is monitored visually by observing skin perfusion color, temperature, and capillary return, particularly during the first few days. The occurrence of a maculopapular rash may indicate acute rejection. The process of rejection in transplant occurs via 2 distinct pathways (direct and indirect).19 In the direct pathway, the recipient αβ-T cells recognize cell surface major histocompatibility complex molecules on donor antigen-presenting cells (APCs) as they migrate out of the graft into native tissue lymph nodes, where donor APCs interact with recipient T cells. The indirect pathway of allorecognition involves the migration of recipient APCs into the allograft and sampling of major histocompatibility complex molecules found within the donor tissues. These systems define different cellular migratory patterns and have also been associated with different types of rejection. The direct pathway has been more closely linked to acute cellular rejection episodes, whereas the indirect pathway has been correlated with chronic rejection. Immunosuppressive protocols in composite tissue allografts, including hand transplants and AWTs, then follow the protocols used in solid-organ transplant (Figure 2).20 The skin, much like the mucosa of the bowel, is the most antigenic component, followed in descending order by muscle, bone, tendon, and cartilage. An increase in total ischemic time of grafts augments the potential for rejection, particularly in epithelial compartments such as the skin and mucosa. Skin changes with abdominal wall rejection are manifest before bowel dysfunction or rejection (Figure 3). This is potentially advantageous, as patients can be treated for rejection before the onset of more serious bowel rejection.21 The distinct sensitivity of skin to rejection that we and others have noted clinically may assist in the identification of early alloresponses, allowing prompt treatment and prevention of eventual rejection of less-sensitive organs such as the intestine or pancreas. The question as to whether patients could receive excess immunosuppression because of skin rejection that would never have progressed to bowel rejection has not yet been fully clarified. There is also some suggestion of a higher incidence of graft-versus-host rejection with AWT. Treatment of rejection includes steroids or antibody treatment (antithymocyte globulins or alemtuzumab) in the case of severe rejection. The treatment of abdominal wall rejection may prevent intestinal rejection, which is a much more difficult issue to address pharmacologically.22
Whatever the approach used, reduction of donor graft size or AWT, it is important to realize that the approaches may not be mutually exclusive to each other and that both approaches can be used as a combination in the same recipient to ensure the success of the transplant procedure. Vascularized composite allotransplant is an established and rapidly expanding field that promotes consideration of the quality of life in patients with severe pathology, such as recalcitrant facial deformity and severe hand dysfunction. It is clear that AWT is a potential solution for patients who have complete loss of domain and are not undergoing visceral organ transplant.23
Despite the potential advantages and good early outcomes, AWT remains an uncommonly performed procedure. This may be partly because of its com-plexity and partly because of the lack of integration of plastic surgery services and transplant services. There are concerns regarding AWT, which has an increased risk of rejection, an increased chance of graft-versus-host disease, and a requirement for prolonged cold ischemic time during the operation. However, the overall incidence of rejection (intestine and skin) appears to be similar to that shown in intestinal transplant patients without AWTs. In addition, the rejection could be determined by sight in AWT; however, intestinal transplant does not have such warning signs. The immunologic effects of combining an AWT with an intestinal transplant are still being investigated. Reconstructive surgeons should be at the forefront of this development and should further the research on immunomodulation and cadaver studies. To tip the scales in favor of isolated AWT, research should be directed toward novel immunosuppression protocols, tolerance induction, and evaluation of immunoregulatory rather than immunosuppressive strategies. With decreased immunosuppression and better outcomes, the indications for this procedure will broaden.24 Prolonged cold ischemic time can be shortened by temporary revascularization in forearm vessels.4
The current experience with AWT is still in its infancy. However, with careful indications, we envision this procedure being used in the future for a larger number of patients with large abdominal wall defects after intestinal transplant.
Volume : 16
Issue : 6
Pages : 745 - 750
DOI : 10.6002/ect.2018.0189
From the Department of Plastic and Reconstructive Surgery, Seoul National
University College of Medicine, Seoul National University Bundang Hospital,
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare. The authors thank Ms. Sun Joo Kim for the preparation of the excellent illustrations and graphic design.
Corresponding author: Seok-Chan Eun, Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si Gyeonggi-do 13620, Republic of Korea
Phone: +82 31 787 7223
Table 1. Abdominal Wall Transplant Performed Worldwide
Table 2. Various Methods for Abdominal Reconstruction
Figure 1. Schematic Design of Donor for Abdominal Wall Transplant Surgery
Figure 2. T-Cell Activation and Site of Action of Immunosuppressive Drugs
Figure 3. Rejection Signs of Abdominal Wall Transplant Showing Skin Changes