Face vascularized composite allografts (FVCA) have helped severe patient disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long‐term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsies for up to an 8 year interval in seven patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte‐mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP‐1 pathway components, JunB and c‐Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid GVHD). Identification of relevant pathways and genes, such as JunB and c‐Fos, may provide new targets into preventative therapies for chronic immune‐mediated changes in vascularized composite allografts.
Due to groundbreaking and pioneering developments in the last century, significant improvements in the care of burn patients have been achieved. In addition to the still valid therapeutic standard of autologous split-thickness skin grafting, various commercially available skin substitutes are currently available. Significant progress in the field of tissue engineering has led to the development of promising therapeutic approaches. However, scientific advances in the field of allografting and transplant immunology are of great importance. The achievement of various milestones over the past decades has provided thought-provoking impulses in the field of skin allotransplantation. Thus, biologically viable skin allotransplantation is still not a part of the clinical routine. The purpose of this article is to review the achievements in burn surgery with regards to skin allotransplantation in recent years.
1 April 2017 in Plastic and Reconstructive Surgery
Background: One of the major challenges in traumatic amputation is the need to keep ischemia time brief (4 to 6 hours) to avoid ischemic damage and enable successful replantation. The current inability to meet this challenge often leads to traumatic limb loss, which has a considerable detrimental impact on the quality of life of patients. Methods: The authors’ team built a portable extracorporeal membrane oxygenator device for the perfusion of amputated extremities with oxygenated acellular solution under controlled parameters. The authors amputated forelimbs of Yorkshire pigs, perfused them ex vivo with acellular Perfadex solution for 12 hours at 10°C in their device, and subsequently replanted them into the host animal. The authors used limbs stored on ice slurry for 4 hours before replantation as their control group. Results: Clinical observation and histopathologic evaluation both demonstrated that there was less morbidity and less tissue damage to the cells during preservation and after replantation in the perfusion group compared with the standard of care. Significant differences in blood markers of muscle damage and tissue cytokine levels underscored these findings. Conclusions: The authors demonstrated the feasibility and superiority of ex vivo hypothermic oxygenated machine perfusion for preservation of amputated limbs over conventional static cold storage and herewith a substantial extension of the allowable ischemia time for replantation after traumatic amputation. This approach could also be applied to the field of transplantation, expanding the potential pool of viable donor vascularized composite allografts.
1 January 2017 in Plastic and Reconstructive Surgery
Background: Face transplantation has emerged as a clinical reality for the restoration of complex facial defects. Critical to the advancement of the burgeoning field of reconstructive transplantation is the quality of the methods used to measure and report the impact of face transplantation on quality of life. Methods: A systematic search using PubMed and EMBASE was conducted for all studies matching the a priori inclusion criteria from 2005 through 2015. Bibliographies of included studies were also reviewed. Two authors (M.A.A and H.K) independently performed screening of titles. Results: The authors identified 17 articles reporting on quality-of-life outcomes among 14 face transplant recipients. Combinations of objective and subjective measures were used to assess quality of life. Instruments used to assess quality of life after face transplantation included over 25 different instruments. Four centers, comprising eight patients, have reported using prospective, systematic data with validated instruments. Overall, there is reported improvement in quality of life after face transplantation. Heterogeneity and a paucity of data between articles preclude a quantitative analysis. Conclusions: Anecdotal and subjective reports of improvements in quality of life after face transplantation constitute the majority of reported outcomes in the English peer-reviewed literature. Improved efforts in methods and standardization of collection and reporting of quality-of-life data after face transplantation are needed to better appreciate the impact of face transplantation on quality of life and justify lifelong immunosuppression and its attendant risks and morbidity.
More than thirty-five facial allograft transplantations (FAT) have been reported worldwide since the pioneering case performed in France in the year 2005. FAT has received tremendous interest by the medical field and the general public while gaining strong support from multiple disciplines as a solution for reconstructing complex facial defects not amenable/responsive to conventional methods. FAT has expanded the frontiers of reconstructive microsurgery, immunology and transplantation, and established its place in the cross section of multiple disciplines. The procedure introduces complex scientific, ethical and societal issues. Patients and physicians are called to deal with a variety of - sometimes everlasting - challenges, such as immunosuppression management and psychosocial hurdles. This review reflects on the surgical and scientific advancements in FAT and milestones reached in the last 12 years. It aims to encourage active discussion regarding the current practices and techniques used in FAT, and suggest future directions that may allow transitioning into the next phase of FAT, which we describe as safe, reliable, and accessible standard operation for selected patients.
1 October 2019 in Plastic and Reconstructive Surgery
Background: A critical barrier to successful limb replantation and allotransplantation is the maximum allowable limb ischemia time of 4 to 6 hours. The current gold standard is to preserve amputated limbs on an ice slurry. Experimental machine perfusion has yielded promising results as an alternative. In particular, hypothermic acellular perfusion has enabled preservation of amputated limbs for up to 12 hours thus far. Methods: Amputated forelimbs of Yorkshire pigs were preserved on static cold storage at 4°C for 4 hours (static cold storage group) or perfused at 8°C for 24 hours (perfusion group) with oxygenated modified STEEN Solution perfusate before replantation. Animals were followed up for 7 days after replantation. Results: Eight animals underwent replantation (cold storage group, n = 4; perfusion group, n = 4). Seventy-five and 100 percent of animals in the static cold storage and perfusion groups survived for 7 days, respectively. Glycogen and adenosine triphosphate remained stable throughout perfusion. Heart and respiratory rate after replantation were increased in the static cold storage group. There was increased damage in muscle biopsy specimens obtained from animals in the static cold storage group after 7 days when compared with those from animals in the perfusion group. Conclusions: Hypothermic acellular ex vivo perfusion of limbs for up to 24 hours enables tissue preservation comparable to that obtained with conventional static cold storage for 4 hours and may reduce muscle damage and systemic reactions on limb replantation. Translation to human limbs may help improve limb replantation and allotransplantation outcomes.