Research status and progress on limb preservation technology / 器官移植

Limb replantation and transplantation is the optimal treatment for traumatic limb amputation. Safe and effective limb preservation is the key factor to determine the success of limb replantation and transplantation. Currently, static cold storage is the gold standard of limb preservation. However, the preservation time is short, which may no longer meet clinical requirements. With rapid development of organ preservation in recent years, novel preservation technologies, such as ultra-low temperature preservation, supercooling preservation and mechanical perfusion preservation, have successively emerged. However, at present, these techniques are primarily applied to the preservation of solid organs rather than composite tissue allografts with blood vessels including limbs. In this article, research status and progress on the application of static cold storage and mechanical perfusion preservation in limb preservation were reviewed, aiming to provide reference for clinical application of limb preservation technology and promote the development of limb replantation and transplantation.

The past, present and future of heart transplantation / 器官移植

Heart transplantation is one of the most effective strategies to treat end-stage heart failure. Multiple challenges, such as difficulty in preservation of heart allograft, rejection and postoperative complications, emerge in heart allotransplantation. After decades of research and practice, most problems have been resolved. Nevertheless, the shortage of donor organs has become increasingly prominent. To alleviate the shortage of donor organs, artificial heart and heart xenotransplantation have captivated attention, and obtained significant progress in recent years. The application of artificial heart in clinical practice has significantly enhanced the survival rate of patients with end-stage heart failure, which is expected to become the standard treatment for end-stage heart failure. Heart xenotransplantation still faces many challenges, which is still far from clinical application. In this article, the history of heart transplantation, development of heart allotransplantation, use of artificial heart and research progress on heart xenotransplantation were reviewed, and the future development direction of heart transplantation was predicted.

Research progress of allogeneic abdominal wall transplantation / 中国修复重建外科杂志

OBJECTIVE@#To summarize the research progress of surgical technique and immunosuppressive regimen of abdominal wall vascularized composite allograft transplantation in animals and clinical practice.@*METHODS@#The literature on abdominal wall transplantation at home and abroad in recent years was extensively reviewed and analyzed.@*RESULTS@#This review includes animal and clinical studies. In animal studies, partial or total full-thickness abdominal wall transplantation models have been successfully established by researchers. Also, the use of thoracolumbar nerves has been described as an important method for functional reconstruction and prevention of long-term muscle atrophy in allogeneic abdominal wall transplantation. In clinical studies, researchers have utilized four revascularization techniques to perform abdominal wall transplantation, which has a high survival rate and a low incidence of complications.@*CONCLUSION@#Abdominal wall allotransplantation is a critical reconstructive option for the difficulty closure of complex abdominal wall defects. Realizing the recanalization of the nerve in transplanted abdominal wall to the recipient is very important for the functional recovery of the allograft. The developments of similar research are beneficial for the progress of abdominal wall allotransplantation.

Diagnostic criteria and research progress on Banff classification of allograft pathology in composite tissue allotransplantation / 器官移植

Composite tissue allotransplantation (CTA) is a novel transplantation discipline to treat functional tissue or limb defects. Since a majority of CTA grafts were vascularized grafts, it is also known as vascularized composite allotransplantation (VCA). The grafts of CTA/VCA consist of two or more types of allogeneic skin, subcutaneous tissue, bone, muscle, nerve and vessel, etc. Most of CTA/VCA grafts contain skin tissues, which possess the highest antigenicity. Acute rejection after transplantation is the primary obstacle leading to CTA/VCA graft failure and primary graft dysfunction. Hence, histopathological characteristics of skin rejection in CTA/VCA grafts have become the primary hotspot. In this article, pathological features of CTA/VCA rejection, Banff classification in 2007 and related research progress were reviewed, aiming to provide reference for the diagnosis and treatment of rejection and other complications of CTA/VCA.

Inducción de tolerancia inmunológica: alotrasplantes compuestos vascularizados y trasplantes de órgano sólido / Immune tolerance induction: vascularized composite allografts and solid organ transplants

Resumen Introducción. La inducción de tolerancia inmunológica solucionaría los problemas asociados con la inmunosupresión de por vida, necesaria para evitar el rechazo de aloinjertos. Objetivos. Revisar aspectos inmunológicos, modelos clínicos utilizados y resultados obtenidos en la tolerancia y comparar los resultados obtenidos con trasplante de órgano sólido y alotrasplante compuesto vascularizado. Materiales y métodos. Se realizó una búsqueda en la base de datos PubMed que arrojó 299 resultados; se revisaron las bibliografías de los artículos y se consultaron las referencias pertinentes. Al final se seleccionaron 83 artículos. Resultados. Existen mecanismos centrales y periféricos para mantener la tolerancia a antígenos propios; en la práctica clínica, la tolerancia central ha sido más utilizada, esto se ha hecho mediante estrategias que utilizan trasplante conjunto de medula ósea. Varios ensayos clínicos, la mayoría en pacientes con trasplante renal, han mostrado resultados prometedores pero inconsistentes. Conclusiones. En trasplantes renales fue posible suspender de forma exitosa la inmunosupresión, mientras que en trasplantes de mano se logró disminuirla considerablemente. El quimerismo inmunológico parece ser indispensable para el desarrollo de tolerancia a aloinjertos, por lo que es necesario desarrollar protocolos para inducir quimerismo mixto persistente.

Abstract Introduction: Immune tolerance induction could solve problems associated with lifelong immunosuppression, necessary to avoid allograft rejection. Objectives: To review immunological aspects, clinical models used and results achieved and to compare the results with solid organ transplantation and vascularized composite allotransplants. Materials and methods: A literature review was made in the PubMed database, yielding 299 results. The bibliography of the articles was reviewed and the pertinent documents were consulted. Finally, 83 articles were selected. Results: There are central and peripheral mechanisms to maintain tolerance to self-produced antigens. In clinical practice, central tolerance has been widely used through strategies that involve bone marrow transplantation. Several clinical trials, mostly in kidney transplant patients, have shown promising but inconsistent results. Conclusions: Immunosuppression was successfully suspended in renal transplantation patients, while its use was reduced considerably in hand transplantation patients. Immunological chimerism seems to be essential to develop tolerance to allografts, so it is necessary to elaborate protocols to induce persistent mixed chimerism.

Anesthetic management of the first forearm transplantation in Korea / 대한마취과학회지

Vascularized composite allotransplantation for the forearm is a complex surgical procedure, requiring multidisciplinary collaboration. It is important to provide optimal blood flow to the grafts, effective immunosuppression, and early rehabilitation for graft survival and good functional outcomes. As ischemia-reperfusion injury and substantial but unquantifiable blood loss are inevitable in this type of surgery, anesthetic management should focus on providing adequate hemodynamic management with proper monitoring, and anesthetic and analgesic strategies to prevent vasoconstriction in the graft. In this paper, we describe the anesthetic management of the first forearm transplantation performed in Korea.

Developments in reconstruction of severe face and neck disfigurement / 上海交通大学学报（医学版）

Severe defects and deformities of face and neck normally arise from burns, tumor extirpation and trauma. They had long been a major therapeutic challenge in the realm of plastic and reconstructive surgery on account of massive involvement of skin and soft tissues, combined composite tissue injuries, high demands on aesthetic and functional outcomes, and scarce suitable reconstructive materials. After an extensive review of literature published recently, this article delineated up-to-date developments in autologous reconstruction and face allotransplantation, especially their indications and limitations in treating these patients. Meanwhile, an outlook on opportunities and challenges of these two treatment modalities was given.

Developments in reconstruction of severe face and neck disfigurement / 上海交通大学学报（医学版）

Severe defects and deformities of face and neck normally arise from burns, tumor extirpation and trauma. They had long been a major therapeutic challenge in the realm of plastic and reconstructive surgery on account of massive involvement of skin and soft tissues, combined composite tissue injuries, high demands on aesthetic and functional outcomes, and scarce suitable reconstructive materials. After an extensive review of literature published recently, this article delineated up-to-date developments in autologous reconstruction and face allotransplantation, especially their indications and limitations in treating these patients. Meanwhile, an outlook on opportunities and challenges of these two treatment modalities was given.

Postoperative care to patients with pancreaticoduodenectomy combined with vascular allotransplantation / 现代临床护理

Objective To probe into methods for postoperatively nursing the patients undergoing pancreaticoduodenectomy combined with vascular allotransplantation. Method The clinical data of postoperative care to 2 patients with pancreatic head carcinoma treated with pancreaticoduodenectomy combined with vascular allotransplantation at the First Affiliated Hospital of Sun Yat-sen University between August 2014 and October 2014 were retrospectively analyzed. Results The two patients lived through the operation, with the operation time of 480 mins, volume of intraoperative blood loss volume of 3000 mL and 600 mL, no complications, hospital stay of 42 days and 27 days. Conclusions The patients undergoing pancreaticoduodenectomy combined with vascular allotransplantation are susceptible to postoperative complications. The nursing care including close observation of disease conditions , drainage tubes care, nutritional care and prevention of complications are critical for the success of operation.

Risk Acceptance and Expectations of Scalp Allotransplantation

BACKGROUND: In scalp allotransplantation, the scalp from a brain-dead donor, including hair, is transferred to a recipient with scalp defects. Opinions differ on the appropriateness of scalp allotransplantation. In order to maintain graft function and cosmetic outcomes, scalp transplantation recipients would need to receive lifelong immunosuppression treatments. The risks of this immunosuppression have to be balanced against the fact that receiving a scalp allotransplant does not extend lifespan or restore a physical function. Therefore, the present study aimed to investigate risk acceptance and expectations regarding scalp allotransplantation in different populations. METHODS: A questionnaire survey study was conducted. A total of 300 subjects participated; survey was conducted amongst the general public (n=100), kidney transplantation recipients (n=50), a group of patient who required scalp reconstruction due to tumor or trauma (n=50), and physicians (n=100). The survey was modified by using the Korean version of the Louisville instrument for transplantation questionnaire. RESULTS: Risk acceptance and expectations for scalp transplantation varied widely across the groups. Kidney transplantation recipients revealed the highest risk acceptance and expectations, whereas the physicians were most resistant to the risks of scalp transplantation. CONCLUSION: Our study demonstrates that, in specific groups, scalp allotransplantation and the need for immunosuppression carries an acceptable risk despite the lack of lifeextending benefits. Our results suggest that scalp allotransplantation can be an acceptable alternative to existing scalp reconstruction surgeries in patients with pre-existing need for immunosuppression.

Vascularized Free Lymph Node Flap Transfer in Advanced Lymphedema Patient after Axillary Lymph Node Dissection / 한국유방암학회지

Lymphedema is a condition characterized by tissue swelling caused by localized fluid retention. Advanced lymphedema is characterized by irreversible skin fibrosis (stage IIIb) and nonpitting edema, with leather-like skin, skin crypts, and ulcers with or without involvement of the toes (stage IVa and IVb, respectively). Recently, surgical treatment of advanced lymphedema has been a challenging reconstructive modality. Microvascular techniques such as lymphaticovenous anastomosis and vascularized lymph node flap transfer are effective for early stage lymphedema. In this study, we performed a two-stage operation in an advanced lymphedema patient. First, a debulking procedure was performed using liposuction. A vascularized free lymph node flap transfer was then conducted 10 weeks after the first operation. In this case, good results were obtained, with reduced circumferences in various parts of the upper extremity noted immediately postoperation.

Inducción de tolerancia en modelo de autotrasplante / Induction of tolerance in allogeneic transplant model

Introduction: Vascularized composite allotransplantation (VCA) involves the transplantation of complex anatomical structures including different kinds of tissue. The aim was to study the effect of a treatment with immature dendritic cells in a model of VCA. Materials and Methods: The rat hind limb allotransplantation model was used. Due to the high antigenic mistmatch Brown Norway rats were used as donors and Lewis rats as recipients. The bone marrow derived immature dendritic cells were cultured under GM-CSF stimuli and donor tissue. The rejection grade and the survival of the graft were assessed. Experimental groups: group I (n = 3): no treatment; Group II (n = 6): tacrolimus 10 mg/kg one day before the transplantation (day -1); Group III (n = 3): tacrolimus 10 mg/kg on day -1 and 6 mg/kg from day 0 to 14, plus intravenous saline infusion on days 7 and 14; Group IV (n = 3): tacrolimus 10 mg/kg on day -1 and 6 mg/kg from day 0 to 14, plus intravenous immature dendritic cells on days 7 and 14. Results: All 15 allografts developed rejection. The mean allograft survival was 14 days in group I, 15 days in group II, 34 days in group III and 58 days in groups IV (p < 0.05). Conclusions: In the rat hind limb allotransplantation model under tacrolimus monotherapy, the treatment with immature bone marrow derived dendritic cells pulsed with alloantigens increases the survival of the graft.

Introducción: El alotrasplante compuesto vascularizado (ACV) involucra el trasplante de estructuras anatómicas complejas que pueden contener distintos tipos de tejidos. El objetivo de este estudio fue evaluar el efecto del tratamiento con células dendríticas inmaduras derivadas de médula ósea del receptor y cargadas con aloantígenos como potencial inductor de tolerancia en un modelo de ACV. Animales y Métodos: Para realizar el modelo de alotrasplante de extremidad posterior de la rata, se utilizaron como donantes ratas Brown Norway y como receptoras ratas Lewis. Las células dendríticas se diferenciaron a partir de precursores de médula ósea que se cargaron con lisado de tejido del donante. Grupos experimentales: Grupo I (n = 3): sin tratamiento; Grupo II (n = 6): tacrolimus 10 mg/kg vía oral el día previo al trasplante (día -1); Grupo III (n = 3): tacrolimus 10 mg/kg el día -1 y 6 mg/kg desde el día 0 al 14 post operatorio como mantención; Grupo IV (n = 3): mismo esquema de tacrolimus que grupo III, pero además infusión intravenosa de células dendríticas los días 7 y 14. Se evaluó la sobrevida de los implantes y el grado de rechazo. Resultados: Los 15 animales trasplantados presentaron rechazo. La sobrevida media del ACV fue de 14 días en el grupo I, 15 días en el grupo II, 34 días en el grupo III y 58 días en el grupo IV (p < 0,05). Conclusión: En un modelo de ACV bajo tratamiento con tacrolimus, la infusión de células dendríticas inmaduras derivadas de médula ósea y pulsadas con aloantígeno aumentan la sobrevida del implante.

Hemifacial Transplantation Model in Rats

BACKGROUND: To refine facial transplantation techniques and achieve sound results, it is essential to develop a suitable animal model. Rat is a small animal and has many advantages over other animals that have been used as transplantation models. The purpose of this study was to describe a rat hemifacial transplantation model and to verify its convenience and reproducibility. METHODS: Animals used in this study were Lewis rats (recipients) and Lewis-Brown Norway rats (donors). Nine transplantations were performed, requiring 18 animals. The hemifacial flap that included the ipsilateral ear was harvested based on the unilateral common carotid artery and external jugular vein and was transferred as a single unit. Cyclosporine A therapy was initiated 24 hours after transplantation and lasted for 2 weeks. Signs of rejection responses were evaluated daily. RESULTS: The mean transplantation time was 1 hour 20 minutes. The anatomy of common carotid artery and external jugular vein was consistent, and the vessel size was appropriate for anastomosis. Six of nine allografts remained good viable without vascular problems at the conclusion of study (postoperative 2 weeks). CONCLUSION: The rat hemifacial transplantation model is suitable as a standard transplantation training model.

Hemifacial Transplantation Model in Rats

BACKGROUND: To refine facial transplantation techniques and achieve sound results, it is essential to develop a suitable animal model. Rat is a small animal and has many advantages over other animals that have been used as transplantation models. The purpose of this study was to describe a rat hemifacial transplantation model and to verify its convenience and reproducibility. METHODS: Animals used in this study were Lewis rats (recipients) and Lewis-Brown Norway rats (donors). Nine transplantations were performed, requiring 18 animals. The hemifacial flap that included the ipsilateral ear was harvested based on the unilateral common carotid artery and external jugular vein and was transferred as a single unit. Cyclosporine A therapy was initiated 24 hours after transplantation and lasted for 2 weeks. Signs of rejection responses were evaluated daily. RESULTS: The mean transplantation time was 1 hour 20 minutes. The anatomy of common carotid artery and external jugular vein was consistent, and the vessel size was appropriate for anastomosis. Six of nine allografts remained good viable without vascular problems at the conclusion of study (postoperative 2 weeks). CONCLUSION: The rat hemifacial transplantation model is suitable as a standard transplantation training model.

Entrenamiento microquirúrgico básico para realizar un modelo animal de alotrasplante compuesto vascularizado / Basic microsurgical training for a vascularized composite allotransplantation animal model

Introduction: rat hind limb transplantation is a complex animal model of vascularized composite allo-transplantation (VCA). A basic microsurgical training is required prior to the implementation of this model. Aim: to propose a training program for the acquisition of basic skills to perform a microsurgical VCA model. Animals and Methods: the training program was conducted in two stages. First, at the dry lab, basic suturing skills with 9-0 to 11-0 nylon sutures were practiced, reproduced from surgical videos performed by experts. In a second stage, at the wet lab using 13 Lewis rats, 6 hind limb microsurgical dissections were performed and the important steps for transplantation were identified: 10 end to end femoral artery anastomoses with 10-0 nylon interrupted suture; 10 end to end femoral vein anastomoses with 10-0 nylon suture; 3 femoral vein interposition in the femoral artery; 6 end to end sciatic nerve neurorrhaphy; 4 femur osteosynthesis with 21g needle and wire cerclage. Anastomotic patency rate and anastomotic surgical time were recorded. Results: arterial and venous patency rate was 100 and 90 percent respectively. Surgical time decreased from 49 to 24 minutes on arterial anastomoses and from 55 to 25 minutes on venous anastomoses after completion of the training program. When a vein interposition was performed, an immediate patency rate of 100 percent was obtained. Conclusion: a successful staged training model of basic microsurgical skills was performed, in order to perform a VCA model.

Introducción: el trasplante de extremidad posterior de la rata es un modelo microquirúrgico de alotras-plante compuesto vascularizado (ACV), que requiere para su implementación de un entrenamiento microquirúrgico básico sistematizado. Objetivo: comunicar un modelo de entrenamiento microquirúrgico básico para adquirir las habilidades y destrezas que permitan realizar un modelo microquirúrgico de ACV Animales y Métodos: el entrenamiento se realizó en 2 etapas: la primera, en laboratorio en seco. A partir de vídeos de microcirugía, se practicó las destrezas para maniobrar suturas de nylon de 9-0 a 11-0. En la segunda etapa in vivo con animales, (13 ratas Lewis), se realizaron: 6 disecciones microquirúrgicas de extremidad posterior para reconocimiento de estructuras anatómicas; 10 anastomosis término-terminal (T-T) de arteria femoral con sutura interrumpida 10-0; 10 anastomosis T-T de vena femoral; 3 interposiciones de vena femoral en arteria femoral; 6 neurorrafias T-T de nervio ciático; 4 fijaciones óseas de fémur con aguja 21 g y cerclaje con alambre. Se evaluó la permeabilidad de las anastomosis y los tiempos quirúrgicos. Resultados: anastomosis arteriales: la permeabilidad inmediata fue de un 100 por ciento. Los tiempos de anastomosis disminuyeron de 49 a 24 min con el entrenamiento. Anastomosis venosas: la permeabilidad inmediata fue de un 90 por ciento. Los tiempos de anastomosis disminuyeron paulatinamente de 55 a 25 min. Interposiciones venosas: se logró una permeabilidad de 100 por ciento. Conclusión: una estrategia de entrenamiento por etapas, es una forma factible de entrenamiento en microcirugía. Este entrenamiento permite obtener una aceptable permeabilidad anastomótica, paso crítico para realizar modelos de ACV.

Review of Current Facial Allotransplantation and Future Aspects

Immunosuppression in composite tissue allotransplantation / 国际外科学杂志

Composite tissue allotransplantation is a new option in reconstruction surgery,but the immunological rejection is accepted as an public medical problem after surgery.As the number of composite tissue allotransplantation increases,postoperative immunosuppression becomes the new hot.This article will illustrate and summarize the progess of postoperative immunesuppression.

Limb Transplantation: Indications and Recent Results

Hand is very important for daily living so most activities is impossible in bilateral amputation of the hand. Hand allotransplantation which was performed firstly in 1998 was epochal method for reconstruction of amputated hand to nearly normal hand. According to long term follow-up beyond 12 years, functional recovery of transplanted hand was inspiring and it was equal or even better than the result of replantation. The satisfactory results of transplantation spread it to worldwide and expand the consensus about the allotransplantation. But immunosuppressive therapy which followed consequently by transplantation induced many complications including infections, metabolic disease and cancer. Transplantation enhanced the quality of life but side effects of immunosuppressant threatened the life itself. So debate is ongoing about the ethical justification and indications of transplantation. This article reviews the recent results of hand transplantation and complications of immunosuppressive therapy.

Rat Hindlimb Allotransplantation with Short-term Immune Suppressants and Dendritic Cell Pretreatment

Prevention of acute rejection in composite tissue allotransplantation without continuous immunosuppression lacks reports in worldwide literature. Recently dendritic cells (DC) gained considerble attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effect of alloantigen-pulsed dendritic cells in induction of survival in a rat hindlimb allograft. We performed hindlimb allotransplantation between donor Sprague-Dawley and recipient Fischer344 rats. Recipient derived dendritic cells were harvested from rat whole blood and cultured with anti-inflammatory cytokine IL-10. Then donor-specific alloantigen pulsed dendritic cells were reinjected into subcutaneous tissue before limb transplantation. Groups: I) untreated (n=6), II) DC injected (n=6), III) Immunosuppressant (FK-506, 2 mg/Kg) injected (n=6), IV) DC and immunouppressant injected (n=6). Graft appearance challenges were assessed postoperatively. Observation of graft appearance, H-E staning, immunohistochemical (IHC) study, and confocal immunofluoreiscece were performed postoperatively. Donor antigen pulsed host dendritic cell combined with short-term immunosuppression showed minimal mononuclear cell infiltration, regulator T cell presence, and could prolong limb allograft survival.

Investigation of Risk Acceptance and Expectations in Hand and Foot Allotransplantations

PURPOSE: Composite tissue allotransplantation is a new therapeutic modality to reconstruct major tissue defects of the head and neck region and extremities. However, there is a serious ethical debate about whether the risks posed by the life-long immunosuppression that a recipient would have to take justify the benefits of receiving this non-life saving procedure. The purpose of this study is to examine differences between expert and non-expert groups in risk acceptance and expectations regarding hand and foot allotransplantations. METHODS: The author conducted a survey of 345 subjects in total (lay public n=110; medical students, n=120; doctors, n=115), using a questionnaire-based instrument, the Louisville Instrument for Transplantation (translated to Korean). RESULTS: Of the three groups studied, risk acceptance was found to be lowest in the doctor group and highest in the non-expert group, and the difference was significant (p < 0.05). The expectations of aesthetic and functional improvement from the procedure, however, were found to be highest in the non-expert group and lowest in the doctor group, and the differences were also significant (p < 0.05). CONCLUSION: The results of this study shows that the three populations have noticeable differences in risk acceptance and expectations regarding hand and foot allotransplantations. Therefore, accurate and sufficient information on these procedures should be provided to patients from both medical and ethical perspectives.